WO2025088126A1

WO2025088126A1 - Topical composition comprising at least two lipids

Info

Publication number: WO2025088126A1
Application number: PCT/EP2024/080240
Authority: WO
Inventors: Jan HOLMBÄCK; Vibhu RINWA
Original assignee: Lipidor AB
Current assignee: Lipidor AB
Priority date: 2023-10-27
Filing date: 2024-10-25
Publication date: 2025-05-01
Anticipated expiration: 2026-04-27

Abstract

The present disclosure relates to a topical composition comprising a carrier; wherein the carrier comprises a phospholipid, a monoglyceride, a fully acylated ester of C₁-C₃ alcohol and a solvent; wherein the composition further comprises at least one pharmaceutically and/or cosmetically active agent. The disclosure is also concerned with a method and a use for delivering an active agent into epidermis and dermis and a composition that is suitable for said delivery, and furthermore with a composition for use in the treatment of a disease or condition of the skin.

Description

TOPICAL COMPOSITION COMPRISING AT LEAST TWO LIPIDS

Technical field

The present disclosure relates to compositions for pharmaceutically and/or cosmetically active agents suitable for cutaneous use.

5

Background

Pharmaceutical compositions for cutaneous administration are of two kinds: one kind aiming at administering a pharmaceutically active agent onto healthy or diseased skin to produce its effect on the skin and/or in one or more layers of the skin, the other kind aiming at the delivery0 of a pharmaceutically active agent through the skin. Cosmetic compositions are designed for cutaneous administration onto healthy skin and for producing their effect on the skin.

Cutaneous administered pharmaceutical or cosmetic products, for instance, target the skin surface, viable epidermis, dermis, or skin appendages such as hair follicles and glands. The skin barrier function, mainly sustained by the stratum corneum, significantly prevents large 5 hydrophilic substances and particulate structures from penetration, which may hamper cutaneous drug delivery.

Topical and/or cutaneous formulations may target specific sites in skin layers, skin appendages, and underlying tissues. They are usually made up of a vehicle, which acts as a carrier for delivery of active substances. Penetration enhancers could be added to the vehicle to facilitate0 permeation through stratum corneum, but further permeation through epidermis and dermis, or through skin appendages, should be controlled to avoid too high flux into the blood system.

Lipids or lipid-like components are commonly used in dosage forms intended for cutaneous administration, e.g., in ointments and creams. Ointments are semisolids containing hydrocarbons, waxes, or vegetable oils as their common ingredients. When applied onto the5 skin a greasy, occlusive layer is formed which gradually interacts with the skin surface.

Ointments are generally poor solvents for the active ingredient, which therefore in many cases is suspended in the formulation rather than dissolved. Creams are generally oil-in-water emulsion systems. They differ compositionally from most ointments and often contain stearic acid, long-chain alcohols and emulsifiers combined with triglyceride oils or hydrocarbons. They form non-occlusive layers on the skin, initially consisting of the particles resulting from the lipid-water interaction in the original emulsion. In both these cases the initial thick layer needs to be rubbed into the skin before the lipids start to become released from the original

5 ointment or cream system. This is especially difficult and painful in skin conditions when the skin has become inflamed and there is also a high risk of spread of bacterial infection. Also, unwanted properties such as oiliness, uneven spread, and difficulty in application of conventional topical formulations such as creams, ointments and foams may lead to nonadherence which likely affects the therapeutic outcome. Therefore, there is an unmet need for0 novel drug delivery formulations which provide for cutaneous drug delivery while side effects and other unwanted effects are reduced compared to formulations in the art.

Disclosure of the invention 5 It is an object of the present invention to at least partly reduce or overcome challenges in the prior art, and provide means for delivery of pharmaceutically or cosmetically active compounds into the skin.

This object is achieved as disclosed herein by the cutaneous use of an inventive composition comprising a carrier and a pharmaceutically and/or cosmetically active compound. These and0 other objects, which will be apparent to a skilled person from the present disclosure, are achieved by the different aspects of the disclosure as defined in the appended claims and as generally disclosed herein.

In a first aspect of the disclosure, there is provided a topical composition comprising a carrier. 5 The carrier comprises at least two lipids selected from the group consisting of a phospholipid; a monoglyceride; and a fully acylated ester of C1-C3 alcohol.

According to the invention, the phospholipid is present in an amount of from about 1.5 to0 about 7.5 % by weight of the carrier. The monoglyceride is present in amount of from about 1.5 to about 7.5 % by weight of the carrier. The fully acylated ester of C1-C3 alcohol is present in an amount of from about 1.5 to about 5 % by weight of the carrier. The total lipid content is from about 3.0 % to about 15 % by weight of the carrier. The carrier comprises a volatile solvent selected from the group consisting of: ethanol and volatile silicone oil; C3-C4 alcohol and volatile silicone oil and ethanol; and C3-C4 alcohol and volatile silicone oil. The composition further comprises at least one pharmaceutically and/or cosmetically active agent selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, anti-inflammatory agents, analgesics, anti-eczema agents, immunomodulators, antidandruff agents, anti-acne agents, anti-seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents.

The present inventors have surprisingly found that the presently disclosed compositions provide for increased or accumulated concentrations of active ingredients in epidermis and/or dermis when applied to the skin. Increased or accumulated concentrations of active ingredients in epidermis and/or dermis are considered advantageous. For example, for treatments intended for local effect in the skin it is advantegous if further permeation into the blood system is avoided, since the risk of adverse events due to systemic exposure thereby is minimized. Furthermore, the concentrations of active agent applied cutaneously (on the skin) do not need to be as high as in the prior art in order to provide for therapeutically and/or cosmetically effective concentrations of active ingredients in epidermis and/or dermis.

Thereby, adverse side effects connected to high concentrations of active agent applied to the skin, for example itching, redness and/or irritation, can be decreased or avoided.

Advantageously, the composition according to the present disclosure is simple to produce on an industrial scale. The composition benefits from the ability of high loading and delivery capacity of an active agent. Furthermore, the compositions disclosed herein provide for a convenient mode of application for the users, for example via a spraying device for application of the composition on the skin of the user. Additionally, when applied to the skin the present compositions leave a smooth and/or soft feeling on the skin. The compositions of the present disclosure are well tolerated by healthy and irritated human skin. As apparent to a person of skill in the art, the ingredients of the composition are all pharmaceutically and/or cosmetically acceptable components. As well known to persons of skill in the art, the skin is made up of three layers, the epidermis, dermis, and the hypodermis. These layers vary in anatomy and function. The layers of the epidermis include stratum corneum as the outer layer, followed by the underlying stratum lucideum, stratum granulosum, stratum spinosum and stratum basale.

As used herein, the term "on the skin" is to be understood as on the outermost layer of the skin, the stratum corneum. A pharmaceutical or cosmetic composition of the invention is designed for cutaneous administration to the skin.

As used herein, the term "into the skin" describes the process of certain compounds to permeate through stratum corneum and into underlying part of the epidermis and/or dermis. A pharmaceutical or cosmetic composition of the invention is designed permeate into epidermis and/or dermis. Permeation into epidermis and/or dermis is also defined as that the compound is "in the skin". For the sake of clarity, permeation of a compound into epidermis in the present context is to be understood as the compound is found in one or more of stratum lucideum, stratum granulosum, stratum spinosum and stratum basale.

In one embodiment, the total lipid content is from about 5.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 5.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 6.0 to about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 8.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 9.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 10.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 11.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 14 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 13 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 12 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 11 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 10 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 9 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 8 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 7 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 5 % by weight of the carrier. In one embodiment, the total lipid content is from about 3 to about 4 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 14 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 13 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 12 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 11 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 10 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 9 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 8 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 7 % by weight of the carrier. In one embodiment, the total lipid content is from about 4 to about 5 % by weight of the carrier.

In one embodiment, the at least two lipids are three lipids. Thus, in this embodiment the composition comprises a phospholipid; a monoglyceride; and a fully acylated ester of C1-C3 alcohol, and the total lipid content is from about 3.0 % to about 15 % by weight of the carrier. In one embodiment, the total lipid content is from about 4.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 5.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 4.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 5.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 4.0 to about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 5.0 to about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 6.0 to about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 8.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 9.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 10.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 11.0 to about 13.0 % by weight of the carrier. In one embodiment, the total lipid content is about 12.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 10.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is from about 11.0 to about 14.0 % by weight of the carrier. In one embodiment, the total lipid content is about 12.0 to about 14.0% by weight of the carrier.

In one embodiment, the carrier comprises from about 1.5 % to about 6.0 % by weight of phospholipid.

In one embodiment, the carrier comprises from about 1.5 % to about 6.0 % by weight of monoglyceride.

In one embodiment, the carrier comprises from about 1.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

In one embodiment, the carrier comprises from about 1.5 % to about 6.0 % by weight of phospholipid, from about 1.5 % to about 6.0 % by weight of monoglyceride, and from about 1.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

In one embodiment, the carrier comprises from about 1.8 % to about 5.0 % by weight of phospholipid. In one embodiment, the carrier comprises from about 2.5 % to about 5.0 % by weight of phospholipid. In one embodiment, the carrier comprises from about 3.0 % to about 5.0 % by weight of phospholipid. In one embodiment, the carrier comprises from about 4.0 % to about 5.0 % by weight of phospholipid. In one embodiment, the carrier comprises about 4.5 % by weight of phospholipid.

In one embodiment, the carrier comprises from about 2.0 % to about 5.5 % by weight of monoglyceride. In one embodiment, the carrier comprises from about 3.0 % to about 5.5 % by weight of monoglyceride. In one embodiment, the carrier comprises from about 4.0 % to about 5.5 % by weight of monoglyceride. In one embodiment, the carrier comprises from about 4.5 % to about 5.5 % by weight of monoglyceride. In one embodiment, the carrier comprises about 5.0 % by weight of monoglyceride.

In one embodiment, the carrier comprises from about 1.5 % to about 2.5 % by weight of fully acylated ester of C1-C3 alcohol.

In one embodiment, the carrier comprises: from about 2.5 % to about 6.0 % by weight of phospholipid, from about 2.5 % to about 6.0 % by weight of monoglyceride, and from about 2.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

In one embodiment, the carrier comprises: from about 3 % to about 6.0 % by weight of phospholipid, from about 3 % to about 6.0 % by weight of monoglyceride, and from about 3 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol. In one embodiment, the carrier comprises: from about 3.5 % to about 6.0 % by weight of phospholipid, from about 3.5 % to about 6.0 % by weight of monoglyceride, and from about 3.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol. In one embodiment, the carrier comprises: from about 4 % to about 6.0 % by weight of phospholipid, from about 4 % to about 6.0 % by weight of monoglyceride, and from about 4 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol. In one embodiment, the carrier comprises: from about 1.8 % to about 5.0 % by weight of phospholipid, from about 2.0 % to about 5.5 % by weight of monoglyceride, and from about 1.5 % to about 2.5 % by weight of fully acylated ester of C1-C3 alcohol.

The carrier according to the present invention comprises at least one volatile solvent selected from the group consisting of ethanol and volatile silicone oil; C3-C4 alcohol and volatile silicone oil and ethanol; and C3-C4 alcohol and volatile silicone oil. An advantage of using a volatile component in the carrier and/or composition is that evaporation of the volatile components(s) from the skin leaves a coherent layer thereon. The so formed layer lacks a greasy feeling, reduces water loss through the skin, and re-establishes the protective skin barrier if compromised. In one embodiment, the solvent is present in an amount of from about 70 % to about 97 % by weight of the carrier. In one embodiment, the solvent is present in in an amount of from about 75 % to about 97 % by weight of the carrier. In one embodiment, the solvent is present in in an amount of from about 80 % to about 95 % by weight of the carrier. In one embodiment, the solvent is present in in an amount of from about 85 % to about 93 % by weight of the carrier.

In one embodiment, the silicone oil is present in an amount of at least 61 %, such as by 62 %, such as by 65 %, such as at least 68 %, such as at least 70 %, such as at least 75 %, such as at least 80 %, or such as at least 85 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 15 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 17 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 20 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 22 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 25 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 27 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 30 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 32 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 35 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 37 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 40 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 42 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 45 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 50 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 52 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 55 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 60 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 61 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 62 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 65 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 68 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 70 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 75 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of at least 80 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of about 85 % by weight of the carrier.

In one embodiment, the silicone oil is present in an amount of from about 10 % to about 90 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 15 % to about 85 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 15 % to about 75 % by weight of the carrier.

In one embodiment, the silicone oil is present in an amount of from about 60 % to about 95 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 60 % to about 90 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 60 % to about 80 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 65 % to about 80 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 68 % to about 78 % by weight of the carrier. In one embodiment, the silicone oil is present in an amount of from about 65 % to about 75 % by weight of the carrier.

In one embodiment, the silicone oil is present in an amount of from about 15 % to about 20 %, or from about 20 % to about 25 %, or from about 25 % to about 30 %; or from about 30 % to about 35 %; or from about 35 % to about 40 %; or from about 40 % to about 45 %; or from about 45 % to about 50 %, or from about 50 % to about 55 %; or from about 55 % to about 60 %; or from about 60 % to about 65 %; or from about 65 % to about 70 %; or from about 70 % to about 75 %, or from about 75 % to about 80 %; or from about 80 % to about 85 %; or from about 85 % to about 95 % by weight of the carrier.

In one embodiment, the silicone oil has a boiling point of 200 °C or less. In one embodiment, the silicone oil has a boiling point of 190 °C or less. In one embodiment, the silicone oil has a boiling point of 180 °C or less. In one embodiment, the silicone oil has a boiling point of 170 °C or less. In one embodiment, the silicone oil has a boiling point of 160 °C or less. In one embodiment, the silicone oil has a boiling point of 150 °C or less. In one embodiment, the silicone oil has a boiling point of 140 °C or less. In one embodiment, the silicone oil has a boiling point of 130 °C or less. In one embodiment, the silicone oil has a boiling point of 120 °C or less. In one embodiment, the silicone oil has a boiling point of 110 °C or less. In one embodiment, the silicone oil has a boiling point of from about 98 °C to about 101 °C. In one embodiment, the silicone oil has a boiling point of from about 50 °C to about 200 °C. In one embodiment, the silicone oil has a boiling point of from about 60 °C to about 160 °C. In one embodiment, the silicone oil has a boiling point of from about 70 °C to about 150 °C. In one embodiment, the silicone oil has a boiling point of from about 80 °C to about 130 °C. In one embodiment, the silicone oil has a boiling point of from about 90 °C to about 110 °C. In one embodiment, the silicone oil has a boiling point of from about 95 °C to about 105 °C. In one embodiment, the silicone oil has a boiling point of from about 98 to about 101 °C.

In one embodiment, the silicone oil is selected from the group consisting of cyclic or straight chain silicone oils with up to six siloxane units. In one embodiment, the silicone oil is selected from the group consisting of decamethylcyclopentasiloxane, decamethyltetrasiloxane, hexamethyldisiloxane and octamethyltrisiloxane. In one embodiment, the silicone oil is selected from the group consisting of decamethyltetrasiloxane, hexamethyldisiloxane and octamethyltrisiloxane. In one embodiment, the silicone oil is decamethylcyclopentasiloxane or hexamethyldisiloxane or octamethyltrisiloxane.

Alcohols, such as ethanol or C3-C4 alcohols are useful solvents or co-solvents and evaporate quickly after application to the skin. In one embodiment, ethanol is present in an amount of from about 10 % to about 80 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 20 % to about 75 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 30 % to about 70 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 40 % to about 70 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 48 % to about 68 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 80 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 75 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 70 % by weight of the carrier.

In one embodiment, ethanol is present in an amount of from about 5 % to about 50 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 5 % to about 40 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 10 % to about 30 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 12 % to about 25 % by weight of the carrier. In one embodiment, ethanol is present in an amount of from about 15 % to about 23 % by weight of the carrier.

In one embodiment, the ethanol is present in an amount of at most 30 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 25 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 20 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 23 % by weight of the carrier. In one embodiment, the ethanol is present in an amount of at most 15 % by weight of the carrier.

In one embodiment, the C3-C4 alcohol is selected from the group consisting of n-propanol, isopropanol, propylene glycol, and mixtures thereof. In one embodiment, the C3-C4 alcohol is present in an amount of from about 5 % to about 50 % by weight of the carrier. In one embodiment, the C3-C4 alcohol is present in an amount of from about 5 % to about 40 % by weight of the carrier. In one embodiment, the C3-C4 alcohol is present in an amount of from about 10 % to about 30 % by weight of the carrier. In one embodiment, the C3-C4 alcohol is present in an amount of from about 12 % to about 25 % by weight of the carrier. In one embodiment, the C3-C4 alcohol is present in an amount of from about 15 % to about 23 % by weight of the carrier.

In one embodiment, ethanol and the C3-C4 alcohol are present in the carrier at a specific ratio. For example, ethanol and the C3-C4 alcohol may be present in a ratio of at least 1:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 2:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 3:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 4:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 5:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 6:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 7:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 8:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of at least 9:10. In one embodiment, ethanol and the C3-C4 alcohol are present in a ratio of about 1:1. In one embodiment, the C3-C4 alcohol and ethanol may be present in a ratio of at least 1:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 2:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 3:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 4:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 5:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 6:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 7:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 8:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of at least 9:10. In one embodiment, the C3-C4 alcohol and ethanol are present in a ratio of about 1:1. In some embodiments relating to the ratio of C3-C4 alcohol: ethanol or the ratio of ethanol: C3-C4 alcohol, the C3-C4 alcohol encompasses all C3-C4 alcohols present in the carrier. For example, when the C3-C4 alcohol is a mixture of at least two of n-propanol, isopropanol, and propylene glycol, the ratio is based on the sum of the weight % of the C3-C4 alcohols.

The compositions of the present invention comprise a monoglyceride, which may act as a penetration enhancer and/or as an emollient.

In one embodiment, the monoglyceride is selected from the group consisting of monoolein and medium chain monoglycerides. The medium chain monoglycerides may be medium chain monoglycerides comprising at least one Cs-Cio monoacylglycerol. In one embodiment, the at least one Cs-Cio monoacylglycerol comprise at least 40 % by weight of said medium chain monoglycerides. In one embodiment, the monoolein comprises at least 50 % by weight of monooleoylglycerol. In one embodiment, the medium chain monoglycerides comprise at least one monoacylglycerol selected from the group consisting of Cs-monoacylglycerol, C10- monoacylglycerol, and a combination thereof.

The compositions of the present invention comprise phospholipid. Phospholipid may act as a solubilizer. Furthermore, the phospholipid may act as a skin barrier recovery agent and/or as a skin barrier strengthening agent.

According to some embodiments, the phospholipid is or comprises natural phosphatidylcholine or synthetic phosphatidylcholine. Natural phosphatidylcholine includes enriched phospholipid from soybeans, sunflower or rapeseed, containing at least 45 % by weight of phosphatidylcholine, the remainder being mainly other polar lipids (such as phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and galactolipids) and acylglycerols (monoacylglycerols, diacylglycerols and triacylglycerols). Lipoid S PC, Lipoid S 100, Lipoid S 80, Lipoid S 75, Lipoid P 75, Lipoid P 100, Lipoid H 90 and Lipoid H 100 are examples of commercially available phospholipids. Examples of preferred commercially available phospholipids are Lipoid S 100, Lipoid S 80 or Lipoid H 100.

In one embodiment, the phospholipid comprises at least 45 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 50 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 55 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 60 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 65 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 70 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 75 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 80 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 85 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 90 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 93 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 94 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 95 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 97 % by weight of phosphatidylcholine. In one embodiment, the phospholipid comprises at least 98 % by weight of phosphatidylcholine.

In one embodiment, the phosphatidylcholine essentially consists of phosphatidylcholine. The term "essentially consists" is intended to be understood as that phosphatidylcholine is the major component of phospholipid. However, phosphatidylcholine may comprise additional components, as discussed above. For example, "essentially consist" in the present context is to be interpreted as the phosphatidylcholine may contain small (minor) amounts of other components. For example essentially consist in the present context is to be interpreted as that phosphatidylcholine corresponds to at least 90 % or for example 94 % by weight of the phospholipid. Examples of products that essentially consists of phosphatidylcholine are Lipoid H 100 and Lipoid S 100.

In one embodiment, the phosphatidylcholine is natural phosphatidylcholine or synthetic phosphatidylcholine.

In one embodiment, the phosphatidylcholine is selected from the group consisting of phosphatidylcholine from soybeans, phosphatidylcholine from sunflower seeds, phosphatidylcholine from rapeseed. In one embodiment, the phosphatidylcholine is selected from the group consisting of phosphatidylcholine from soybeans and phosphatidylcholine from sunflower seeds. In one embodiment, the phosphatidylcholine is selected from as the group consisting of phosphatidylcholine from soybeans. In one embodiment, the phospholipid is selected from the group consisting of Lipoid S PC, Lipoid S 100, Lipoid S 80, Lipoid S 75, Lipoid P 75, Lipoid P 100, Lipoid H 90 and Lipoid H 100. In one embodiment, the phospholipid is selected from the group consisting of Lipoid S 100, Lipoid S 80 and Lipoid H 100. In one embodiment, the phospholipid is selected from the group consisting of Lipoid S 100.

In one embodiment, the synthetic phosphatidylcholine is selected from the group consisting of dimyristoyl phosphatidylcholine and dioleoyl phosphatidylcholine.

The compositions of the present invention comprise a fully acylated ester of C1-C3 alcohol, which may act as a penetration enhancer and/or as an emollient. In one embodiment, the fully acylated ester of C1-C3 alcohol is an acyl ester of methanol, ethanol, n-propanol or isopropanol. In one embodiment, the fully acylated ester of C1-C3 alcohol is a diacyl ester of ethylene glycol or propylene glycol. In one embodiment, the fully acylated ester of C1-C3 alcohol is a triacyl ester of glycerol. In one embodiment, an acyl group of the fully acylated ester of C1-C3 alcohol comprises Ce-Cis saturated or monounsaturated fatty acids. In one embodiment, the fully acylated ester of C1-C3 alcohol is selected from the group consisting of isopropyl myristate, ethyl oleate, medium chain triglycerides, isopropyl palmitate, and almond oil. In one embodiment, the fully acylated ester of C1-C3 alcohol is selected from the group consisting of isopropyl myristate, ethyl oleate, medium chain triglycerides, and almond oil. In one embodiment, the fully acylated ester of C1-C3 alcohol is isopropyl myristate. In one embodiment, the fully acylated ester of C1-C3 alcohol is isopropyl palmitate. In one embodiment, the fully acylated ester of C1-C3 alcohol is almond oil. The skilled person appreciates that almond oil comprises, or essentially consists of triglycerides, essentially constituted by the following fatty acids: oleic acid (in an amount of approximately 68 %) (C18:l), stearic acid (C18:0), linoleic acid (C18:2), palmitoleic acid (C16:l) and palmitic acid (C16:0).

A carrier according to the present disclosure may be defined by its specific amounts of the components therein. In some embodiments, these components comprises or consists of: phospholipid, fully acylated C1-C3 alcohol, monoglyceride, silicone oil, and alcohol. The specific amount may be defined in %w/w. The following represents a group of some basic carriers disclosed herein (the specific amount are defined in %w/w): 5.1 % Lipoid S100, 7.6 % isopropyl myristate, 7.8 % medium chain monoglycerides, 59.6 % decamethylcyclopentasiloxane, 19.9 % ethanol; 7.6 % Lipoid S100, 6.8 % isopropyl myristate, 6.3 % medium chain monoglycerides,

59.3 % decamethylcyclopentasiloxane, 20.0 % ethanol; 10.5 % Lipoid S100, 5.1 % isopropyl myristate, 4.9 % medium chain monoglycerides, 59.6 % decamethylcyclopentasiloxane, 20.0 % ethanol; 15.1 % Lipoid S100, 2.5 % isopropyl myristate, 2.4 % medium chain monoglycerides,

59.8 % decamethylcyclopentasiloxane, 20.2 % ethanol; 10.1 % Lipoid S100, 2.5 % isopropyl myristate, 2.5 % medium chain monoglycerides, 65.0 % decamethylcyclopentasiloxane, 19.9 % ethanol; 10.1 % Lipoid S100, 0.0 % isopropyl myristate, 2.6 % medium chain monoglycerides, 67.5 % decamethylcyclopentasiloxane, 19.9 % ethanol; 9.9 % Lipoid S100, 0.0 % isopropyl myristate, 0.0 % medium chain monoglycerides, 69.0 % decamethylcyclopentasiloxane, 21.1 % ethanol; 5.2 % Lipoid S100, 2.4 % isopropyl myristate, 2.4 % medium chain monoglycerides,

69.8 % decamethylcyclopentasiloxane, 20.1 % ethanol; 5.2 % Lipoid S100, 0.0 % isopropyl myristate, 2.7 % medium chain monoglycerides, 72.1 % decamethylcyclopentasiloxane, 20.0 % ethanol; 5.2 % Lipoid S100, 2.6 % isopropyl myristate, 0.0 % medium chain monoglycerides,

72.4 % decamethylcyclopentasiloxane, 19.8 % ethanol; 0.0 % Lipoid S100, 5.0 % isopropyl myristate, 5.0 % medium chain monoglycerides, 70.0 % decamethylcyclopentasiloxane, 20.0 % ethanol; 1.0 % Lipoid S100, 4.0 % isopropyl myristate, 0.0 % medium chain monoglycerides, 75.0 % decamethylcyclopentasiloxane, 19.9 % ethanol; 1.1 % Lipoid S100, 0.0 % isopropyl myristate, 4.0 % medium chain monoglycerides, 74.9 % decamethylcyclopentasiloxane, 20.1 % ethanol; 2.5 % Lipoid S100, 1.1 % isopropyl myristate, 1.1 % medium chain monoglycerides, 75.3 % decamethylcyclopentasiloxane, 19.9 % ethanol; 2.0 % Lipoid S100, 2.2 % isopropyl myristate, 2.0 % medium chain monoglycerides, 73.3 % decamethylcyclopentasiloxane, 20.6 % ethanol; 9.9 % Lipoid S100, 4.9 % isopropyl myristate, 5.0 % medium chain monoglycerides, 60.9 % decamethylcyclopentasiloxane, 19.4 % ethanol; 9.6 % Lipoid S100, 4.9 % isopropyl myristate, 4.9 % medium chain monoglycerides, 59.9 % decamethylcyclopentasiloxane, 20.7 % ethanol; 2.1 % Lipoid S100, 2.0 % isopropyl myristate, 2.1 % medium chain monoglycerides, 74.0 % hexamethyldisiloxane, 19.9 % ethanol; 4.5 % Lipoid S100, 2.1 % isopropyl myristate, 4.0 % medium chain monoglycerides, 69.0 % hexamethyldisiloxane, 20.4 % ethanol; 4.5 % Lipoid S100, 2.0 % isopropyl myristate, 2.1 % medium chain monoglycerides, 71.7 % hexamethyldisiloxane, 19.8 % ethanol; 1.9 % Lipoid S100, 1.9 % isopropyl myristate, 4.0 % medium chain monoglycerides, 71.3 % hexamethyldisiloxane, 20.9 % ethanol; 1.0 % Lipoid

5100. 1.1 % isopropyl myristate, 1.2 % medium chain monoglycerides, 75.4 % hexamethyldisiloxane, 21.2 % ethanol; 3.1 % Lipoid S100, 0.0 % isopropyl myristate, 0.0 % medium chain monoglycerides, 75.9 % hexamethyldisiloxane, 21.0 % ethanol;

10.1 % Lipoid S100, 5.0 % isopropyl myristate, 5.0 % medium chain monoglycerides, 60.2 % hexamethyldisiloxane, 19.7 % ethanol; 3.9 % Lipoid S100, 2.2 % isopropyl myristate, 3.9 % medium chain monoglycerides, 69.9 % hexamethyldisiloxane, 20.1 % ethanol; 3.9 % Lipoid S100, 2.2 % isopropyl myristate, 3.9 % medium chain monoglycerides, 70.0 % hexamethyldisiloxane, 20.0 % ethanol; 4.5 % Lipoid S100, 2.2 % isopropyl myristate, 5.1 % medium chain monoglycerides, 68.1 % hexamethyldisiloxane, 20.1 % ethanol; 3.9 % Lipoid S100, 2.2 % isopropyl myristate, 3.9 % medium chain monoglycerides, 69.9 % hexamethyldisiloxane, 20.1 % ethanol; 10.5 % Lipoid H100 , 5.3 % isopropyl myristate, 5.3 % medium chain monoglycerides, 60.5 % decamethylcyclopentasiloxane, 18.4 % isopropyl alcohol; 6.9 % Lipoid S100, 3.2 % medium chain triglycerides, 4.3 % Monoolein, 65.5 % hexamethyldisiloxane, 20.1 % isopropyl alcohol; 3.25 % Lipoid S100, 2.3 % medium chain triglycerides , 6.0 % medium chain monoglycerides, 72.2 % hexamethyldisiloxane, 16.3 % ethanol; 1.0 % Lipoid S100, 1.0 % isopropyl myristate, 1.0 % medium chain monoglycerides, 75.0 % hexamethyldisiloxane, 22.0 % ethanol; 3.9 % Lipoid S100, 2.2 % isopropyl myristate, 3.9 % medium chain monoglycerides, 68.0 % hexamethyldisiloxane, 22.0 % ethanol; and 4.3 % Lipoid S80, 2.8 % Ethyl oleate, 6.5 % Monoolein, 70.4 % hexamethyldisiloxane, 16.0 % ethanol. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of anti-psoriatic agents, such as vitamin D analogs like calcipotriol, calcitriol, cholecalciferol, taca Icitol, pa rica Icitol, a Ifaca Icidol, doxercalciferol, fa leca Icitriol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof and other anti-psoriatic agents such as roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antibiotic agents, such as dapsone, dicloxacillin, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-fungal agents, such as ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antiviral agents, such as acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet and docosanol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-inflammatory agents, such as curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; analgesics, such as salicylic acid, ibuprofen, capsaicin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-eczema agents, such as dexpanthenol, corticosteroids, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; calcineurin inhibitors/immunomodulators, such as pimecrolimus and tacrolimus, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-dandruff agents, such as ketoconazole and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-acne agents, such as retinoids like tretinoin, isotretinoin, adapalene, tazarotene, trifarotene, and other agents like clascoterone, niacinamide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-seborrheics, such as selenium sulfide, zinc pyrithione, and salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; local anesthetics, such as benzocaine, lidocaine, prilocaine, tetracaine and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; corticosteroids, such as betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; vitamins, such as vitamin B complex, vitamin C, vitamin D, calcium pantothenate, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; keratolytic agents, such as citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, sulphur and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-psoriatic agent selected from the group consisting of calcipotriol, calcitriol, cholecalciferol, tacalcitol, pa ricalcitol, alfacalcidol, doxercalciferol, falecalcitriol, roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-psoriatic agent. In one embodiment, the anti-psoriatic agent is a vitamin D analogue. In one embodiment, the at least one active agent is at least one anti-psoriatic agent selected from the group consisting of calcipotriol, calcitriol, cholecalciferol, tacalcitol, paricalcitol, alfacalcidol, doxercalciferol, falecalcitriol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least one active agent is at least one anti-psoriatic agent selected from the group consisting of roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least one active agent is at least one antibiotic agent selected from the group consisting of dapsone, dicloxaci II i n, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-fungal agent selected from the group consisting of ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one antiviral agent selected from the group consisting of acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet and docosanol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-inflammatory agent selected from the group consisting of curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one analgesic agent selected from the group consisting of as salicylic acid, ibuprofen, capsaicin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-eczema agent selected from the group consisting of dexpanthenol, corticosteroids, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one calcineurin inhibitor and/or immunomodulator selected from the group consisting of pimecrolimus, tacrolimus, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-dandruff selected from the group consisting of ketoconazole and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least one active agent is at least one anti-acne selected from the group consisting of retinoids, clascoterone, niacinamide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the retinoid is selected from the group consisting of tretinoin, isotretinoin, adapalene, tazarotene, trifarotene and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one anti-seborrheic selected from the group consisting of selenium sulfide, zinc pyrithione, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one local anesthetic selected from the group consisting of benzocaine, lidocaine, prilocaine, tetracaine and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one corticosteroid selected from the group consisting of betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one vitamin selected from the group consisting of vitamin B complex, vitamin C, vitamin D, calcium pantothenate, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one active agent is at least one keratolytic agent selected from the group consisting of citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, sulphur and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, adapalene, a Ifaca Icidol, azelaic acid, benzocaine, betamethasone, calcipotriol, calcitriol, calcium pantothenate, capsaicin, cephalosporin, cholecalciferol, ciclopirox, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, dapsone, deflazacort, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, dicloxacillin, docosanol, doxercalciferol, doxycycline, econazole, erythromycin, falecalcitriol, famciclovir, fluconazole, fl unisolide, fluocinolone, foscarnet, fusidic acid, ganciclovir, gentamicin, glycolic acid, hydrocortisone, ibuprofen, indomethacin, isotretinoin, itraconazole, ketoconazole, ketoprofen, lactic acid, lidocaine, loteprednol, metronidazole, miconazole, minocycline, mometasone, mupirocin, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prednisone, prilocaine, quercetin, ribavirin, roflumilast, salicylic acid, selenium sulfide, sulfacetamide sodium, sulphur, taca Icitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, valaciclovir, vidarabine, vitamin B complex, vitamin C, vitamin D, zidovudine, zinc pyrithione, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, a Ifaca Icido I, betamethasone, calcipotriol, calcitriol, capsaicin, cholecalciferol, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, docosanol, doxercalciferol, econazole, erythromycin, fa leca Icitriol, flunisolide, fusidic acid, hydrocortisone, ibuprofen, indomethacin, ketoconazole, ketoprofen, lactic acid, lidocaine, metronidazole, miconazole, minocycline, mometasone, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prilocaine, ribavirin, roflumilast, salicylic acid, selenium sulfide, taca Icitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, vitamin C, vitamin D, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one cosmetically active agent is selected from the group consisting of calcium pantothenate, capsaicin, citric acid, curcumin, dexpanthenol, docosanol, glycolic acid, lactic acid, niacinamide, quercetin, salicylic acid, selenium sulfide, sulphur, urea, vitamin B complex, vitamin C, vitamin D, zinc pyrithione, and cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is calcipotriol, calcitriol, cholecalciferol, tacalcitol, paricalcitol, alfacalcidol, doxercalciferol, falecalcitriol, roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol, dapsone, dicloxacillin, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet, docosanol, curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, salicylic acid, ibuprofen, capsaicin, dexpanthenol, corticosteroids, pimecrolimus, tacrolimus, ketoconazole, tretinoin, isotretinoin, adapalene, tazarotene, trifarotene, clascoterone, niacinamide, selenium sulfide, zinc pyrithione, salicylic acid benzocaine, lidocaine, prilocaine, tetracaine, betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, vitamin B complex, vitamin C, vitamin D, calcium pantothenate, citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, or sulphur.

As apparent to a person of skill in the art, the octanol-water partition coefficient K_ow gives an indication of the relationship between lipophilicity and hydrophilicity of a compound and provides an estimate of the solubility in a carrier. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent has a log K_ow value within a range of 1-8. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent has a log Kow value within a range of 2-5. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent has a log K_ow value within a range of a range of -2-8, such as within a range of -2-7, such as within a range of -1.8-5. A person of skill in the art knows how to determine the log K_ow value of a compound. A person of skill in the art knows how to find a log Kow reference value for a compound. Log K_ow values can for example be found on PubChem (https://pubchem.ncbi.nlm.nih.gov/).

In one embodiment, the composition comprises at least two active agents. This is beneficial when a combination treatment is wanted or may prove useful in treatment of a condition or a disease. For example, tables 3-5 below describe specific embodiments of the present disclosure wherein the composition comprises two active agents. The skilled person appreciates that at least two active agents can be combined in a functional composition according to the present disclosure. In one embodiment, the at least two active agents are selected from agents of the same functional group. As a non-limiting example, said at least two agents may be anti-psoriatic agents. In another embodiment, said at least two agents are selected from different functional groups. As a non-limiting example, one agent is an anti- psoriatic agent, and one agent may be an anti-inflammatory agent such as a corticosteroid.

In one embodiment, the at least two active agents are selected from the group consisting of calcipotriol and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of tazarotene and mometasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; In one embodiment, the at least two active agents are selected from the group consisting of roflumilast and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from group consisting of trifarotene and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of tacrolimus and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of capsaicin and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of hydrocortisone and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of trifarotene and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of dexpanthenol and urea and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of lidocaine and prilocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of hydrocortisone and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of ketoconazole and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the at least two active agents are selected from the group consisting of fusidic acid and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least two active agents are calcipotriol and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or tazarotene and mometasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or roflumilast and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; trifarotene and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; tacrolimus and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or capsaicin and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or hydrocortisone and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or trifarotene and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or dexpanthenol and urea and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or lidocaine and prilocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or hydrocortisone and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or ketoconazole and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or fusidic acid and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least two active agents are selected from the group consisting of calcipotriol and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of tazarotene and mometasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of roflumilast and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; the group consisting of trifarotene and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; the group consisting of tacrolimus and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of capsaicin and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least two active agents are calcipotriol and betamethasone. In one embodiment, the betamethasone and calcipotriol are present in a ratio of at least 4:1, such as at least 5:1, such as at least 6:1, such as at least 7:1, such as at least 8:1, such as at least 9:1, such as at least 10:1, such as at least 20:1.

Disclosed herein are pharmaceutical and/or cosmetic compositions, for example the following group of such compositions: 0.005 %(w/w) Calcipotriol in carrier AC-123; 0.10 %(w/w) Betamethasone dipropionate in carrierAC-124; 0.10 %(w/w) Mometasone furoate in carrier AC-124; 0.3 %(w/w) Roflumilast in carrier AC-202; 1.0 %(w/w) Tapinarof in carrier AC-131; 0.1 %(w/w) Tazarotene in carrier AC-129; 0.005 %(w/w) Trifarotene in carrier AC-129; 0.1 %(w/w) Capsaicin in carrier AC-206; 1.5 %(w/w) Minocycline in carrier AC-109; Clindamycin in carrier AC-109; 2.0 %(w/w) Fusidic acid, sodium salt in carrier AC-202; Terbinafine in carrier AC-131; 0.3 %(w/w) Tacrolimus in carrier AC-131 + Lactic acid 2.0%; 2.6 %(w/w) Ketoprofen in carrier AC-125; 5.0 %(w/w) Lidocaine in carrier AC-203; 5.0 %(w/w) Prilocaine in carrier AC-203; 2.1 %(w/w) Salicylic acid in carrier AC-204; 0.3 %(w/w) Curcumin in carrier AC-205; 4.8 %(w/w) Dexpanthenol in carrier AC-206; and 3.2 %(w/w) Urea in carrier AC-206. The carrier code AC- XXX wherein XXX is the number is found in table 1 below. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.001 % to about 20 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.02 % to about 15 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.05 % to about 10 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.05 % to about 5 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.05 % to about 3 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.05 % to about 1 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.001 % to about 20 % by weight of the composition.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.002 % to about 0.01 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.01 % to about 0.05 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.05 % to about 0.20 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.20 % to about 0.25 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.25 % to about 0.30 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 0.5 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 1.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 1.0 % to about 1.4 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 1.8 % to about 1.9 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 2.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 2.0 % to about 2.6 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 3.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 5.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 8.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 10.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 15.0 % by weight of the composition. In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is present in an amount of about 20.0 % by weight of the composition.

The composition is typically free of water, although water may be present in a very small amount, e.g. as a minor part of a component described herein. The water content may be 5 % or less by weight of the composition, such as 3 % or less, such as 2 % or less, or 1 % or less, or 0.5 % or less, such about 0 %. Thus, the composition may be essentially free of water. The skilled person appreciates that the term "essentially free of water" does not exclude residual amounts of water, such as residual water originating from the components of the composition. Thus, the composition does not require the components therein to be anhydrous. The composition is essentially not miscible with water and will instead form a two-phase system when water is added in higher amounts, such as when water is added to be present in an amount of over 5 % by weight, such as over 10 % by weight of the composition. In one embodiment, the composition comprises water in an amount of at maximum 5 % by weight of the carrier. In one embodiment, the composition comprises water in an amount of at maximum 2 % by weight of the carrier. In one embodiment, the composition comprises water in an amount of at maximum 1 % by weight of the carrier. In one embodiment, the composition comprises water in an amount of at maximum 0.5 % by weight of the carrier. In one embodiment, the carrier is essentially water free. In one embodiment, the composition is essentially water free.

In one embodiment, the composition further comprises at least one pharmaceutically acceptable excipient and/or at least one cosmetically acceptable excipient. In one embodiment, the excipient is selected from the group consisting of lactic acid, triethanolamine, oleic acid, triisopropanolamine and malic acid.

According to the present disclosure, the application of a composition as disclosed herein may change the pH of the skin area to which the composition is applied. The skilled formulator appreciates that one should avoid application of compositions with a pH value higher than 7 onto the skin. As such, upon application of a composition according to the present invention, the pH value of the skin may be lowered to at a maximum pH value of 7.0, such as at a maximum pH value of 6.5, such as at a maximum pH value of 6.0, such as at a maximum pH value of 5.0, such as at a maximum pH value of 5.5, such as at a maximum pH value of 5.0, such as at a maximum pH value of 4.5, such as at a maximum pH value of 4.0, such as at a maximum pH value of 3.5, and may reach a pH value of about 3. After application, the pH value of the skin will revert to normal. The skilled person appreciates that the normal pH of the skin is between 4.7 and 5.75.

In one embodiment, the composition further comprises a pH modulator. A pH modulator may be an acidifying agent, an alkalizing agent and/or a buffering agent. In one embodiment, the pH modulator is present in an amount of from about 0.1 % to about 20 %, such as from about 0.2 % to about 5 %, such as from about 1 % to about 4 %, such as from about 2 % to about 3 %; or such as from about 5 % to about 20 %, such as from about 5 % to about 15 %, such as from about 5 % to about 11 % by weight of the carrier. In one embodiment, the pH modulator is selected from the group consisting of lactic acid, citric acid, glycolic acid, acetic acid, triethanolamine, oleic acid, triisopropanolamine, and malic acid. In one embodiment, the pH modulator is lactic acid.

In one embodiment, the composition further comprising at least one keratolytic agent. In one embodiment, the keratolytic agent is present in an amount of from about 0.5 % to about 10 %, or from about 1 % to about 5 %, or from about 1 % to about 4 %, or from about 1 % to about 3 %; or from about 3 % to about 5 %; or from about 5 % to about 8 % by weight of the carrier. In one embodiment, the keratolytic agent is selected from the group consisting of glycolic acid, lactic acid, malic acid, salicylic acid, allantoin, urea, and sulphur. In one embodiment, the keratolytic agent is lactic acid.

The present compositions are clear (transparent) and physically stable solutions of low viscosity, which are easily applicable by spraying e.g. to the skin of a subject. The compositions and carriers are single-phase, homogeneous liquids that are stable, at room temperature, for an extended period of time, such as for at least 1 day, such as for at least 1 week, such as for at least 2 weeks, such as for at least 5 weeks, such as for at least 10 weeks, such as for at least 15 weeks, such as for at least 20 weeks, such as for at least 25 weeks, such as for at least 30 weeks, such as for at least 40 weeks, such as for at least 50 weeks, such as for at least 1 year, such as for at least 1.5 years, such as for at least 2 years, such as for at least 3 years, such as for at least 4 years, such as for at least 5 years. By "stable" is meant that the composition does not exhibit precipitation, cloudiness, haziness or phase separation. In one embodiment, the composition is a single-phased homogeneous liquid at room temperature (20 °C).

The carriers and compositions disclosed herein are intended administered in the form of a spray, a drop or as a solution. Thus, there is provided a composition as disclosed herein, adapted or formulated for administration in the form of a spray, a drop or a solution.

In one embodiment, the composition further comprises a co-solvent. The use of a co-solvent in the presently disclosed composition may prove useful in solubilization of the at least one active agent. In one embodiment, the co-solvent is selected from the group consisting of propylene glycol, oleic acid, glycerol, polyethylene glycol, and diethylene glycol monoethyl ether. In one embodiment, the co-solvent is selected from the group consisting of as the group consisting of propylene glycol, oleic acid, and glycerol.

In one embodiment, the co-solvent is present in an amount of at most 20 % by weight of the carrier. In one embodiment, the co-solvent is present in an amount of at most 15 % by weight of the carrier. In one embodiment, the co-solvent is present in an amount of at most 10 % by weight of the carrier. In one embodiment, the co-solvent is present in an amount of at most 5 % by weight of the carrier. In one embodiment, the composition further comprises an antioxidant. An antioxidant of the invention is any additional component that inhibits other components from degrading due to oxidation. Antioxidants are exemplified by, but not limited to, reducing agents such as thiols, ascorbic acid, or polyphenols, free radical scavengers such as tocopherols (Vitamin E) and tocotrienols, sequestering agents such as EDTA and phosphonates, or organic acids such as acetic acid, citric acid, glycolic acid or lactic acid any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. Preferred antioxidants are a-tocopherol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate and propyl gallate. In one embodiment, the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate and propyl gallate, thiols, ascorbic acid, polyphenols, tocopherols, tocotrienols, EDTA, phosphonates, acetic acid, citric acid, glycolic acid, lactic acid, and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, the antioxidant is selected from the group consisting of alpha-tocopherol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate, and propyl gallate.

The active agents described herein may form pharmaceutically and/or cosmetically acceptable salts which are within the scope of the present invention. Pharmaceutically and/or cosmetically acceptable salts are known by a person of skill in the art. For example, suitable salts according to the invention, such as those formed with organic or inorganic acids or bases. In particular, suitable salts formed with acids according to the invention, such as those formed with mineral acids, strong organic carboxylic acids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which are unsubstituted or substituted, for example, by halogen, such as saturated or unsaturated dicarboxylic acids, such as hydroxycarboxylic acids, such as amino acids, or with organic sulfonic acids, such as (Cl- C4)a I kyl or aryl sulfonic acids which are unsubstituted or substituted, for example by halogen. Pharmaceutically and/or cosmetically acceptable acid addition salts, such as those formed from hydrochloric, hydrobromic, sulphuric, nitric, citric, tartaric, acetic, phosphoric, lactic, pyruvic, acetic, propionic, trifluoroacetic, succinic, perchloric, fumaric, maleic, glycolic, gluconic, lactic, salicylic, oxaloacetic, methanesulfonic, ethanesulfonic, p-toluenesulfonic, formic, benzoic, malonic, naphthalene-2-sulfonic, benzenesulfonic, isethionic, ascorbic, malic, furoic, phthalic, aspartic, and glutamic acids, lysine and arginine.

Pharmaceutically and/or cosmetically acceptable base salts, such as ammonium salts, alkali metal salts, for example those of potassium and sodium, alkaline earth metal salts, for example those of calcium and magnesium, and salts with organic bases, for example dicyclohexylamine, N-methyl-D-glucamine, morpholine, thiomorpholine, piperidine, pyrrolidine, a mono, di- or tri lower alkylamine, for example ethyl, tertbutyl, diethyl, diisopropyl, triethyl, tributyl or dimethylpropylamine, or a mono- , di- or trihydroxy lower alkylamine, for example mono-, di- or triethanolamine. Corresponding internal salts may furthermore be formed. Specifically preferred salts according to the present disclosure are in the group consisting of calcium, potassium, sodium, hydrochloride, phosphate, sulphate, gluconate, diethylamine and ammonium.

According to the invention, the compositions described herein provide for intermediate permeation of an active agent into the skin. That is, the active agent will pass the stratum corneum, while accumulating in the underlying epidermis and/or dermis. To clarify, the epidermis underlying the stratum corneum encompasses the stratum lucideum, stratum granulosum, stratum spinosum and stratum basale. Intermediate permeation is further discussed in Examples 2a and 2b below. In one embodiment, the active agent is capable of permeation through stratum corneum. Permeation of an active agent through stratum corneum is further discussed in Examples 4a, 4b, and 7 below. In one embodiment, the active agent is capable of permeation into underlying epidermis and/or dermis. Accumulation of the active agent in epidermis and dermis is further discussed in Example 3 below. In one embodiment, the active agent is capable of permeation into one or more of stratum lucideum, stratum granulosum, stratum spinosum and stratum basale and/or dermis.

In a second aspect, there is provided a cutaneous composition comprising a carrier, which carrier comprises at least two lipids selected from the group consisting of: a phospholipid; a monoglyceride; and a fully acylated ester of C1-C3 alcohol.

According to the second aspect, the phospholipid is present in an amount of from about 1.5 to about 7.5 % by weight of the carrier, the monoglyceride is present in amount of from about 1.5 to about 7.5 % by weight of the carrier, and the fully acylated ester of C1-C3 alcohol is present in an amount of from about 1.5 to about 5 % by weight of the carrier. The total lipid content is from about 3.0 % to about 15 % by weight of the carrier. The carrier comprises a volatile solvent selected from the group consisting of: ethanol and volatile silicone oil; C3-C4 alcohol and volatile silicone oil and ethanol; and C3-C4 alcohol and volatile silicone oil. The composition further comprises at least one pharmaceutically and/or cosmetically active agent selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, anti-inflammatory agents, analgesics, anti-eczema agents, immunomodulators, antidandruff agents, anti-acne agents, anti-seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents. The carrier of the second aspect is as defined in any one the embodiments of the first aspect. Importantly, the carrier is suitable for delivering said at least one active agent through stratum corneum. As used herein, "suitable for delivering" is intended to mean that the carrier is able to carry an effective amount of the active agent through stratum corneum. This is specifically shown for some compositions of the invention. For example, Example 2 shows permeation through an artificial membrane of an active agent, which confirms that the compositions of the present invention are able to permeate through such membrane. In addition, Example 3 shows permeation through stratum corneum and into dermis and epidermis of two active agents. The results confirm that the compositions of the present invention are able to permeate stratum corneum and accumulate in dermis and epidermis. Example 4 confirms these findings by studying the availability of two active agents in dermis and/or epidermis after application of compositions according to the invention to the skin, indicating more effective delivery of active agent using inventive compositions.

The skilled person appreciates that an "effective amount" of an at least one active agent refers to an amount of agent needed to provide a therapeutic effect in a subject in need thereof in the context of therapy. The skilled person appreciates that an "effective amount" of an at least one active agent refers to an amount of agent needed to provide a cosmetic effect in a subject in need thereof in the context of cosmetic and non-therapeutic application. As discussed in relation to the general advantages of the compositions disclosed herein, the carrier is suitable for delivering said at least one active agent in the sense that it leaves a smooth and/or soft feeling on the skin when applied to the skin. The compositions of the present disclosure are suitable for said delivery since they are well tolerated by healthy and irritated human skin. As such, "suitable for delivery" encompass that the carriers of the invention do not give rise to any significant adverse side effects resulting from the carrier as such; and encompass that the carriers of the invention are not irritating to the skin, i.e., do not give rise to any or any significant irritation (for example but not limited to redness, a sense of itching, or dryness) resulting from the carrier as such.

In a third aspect, there is provided a composition according to the first aspect, for use in the treatment of a disease, a disorder or a condition of the skin.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, anti-inflammatory agents, analgesics, anti-eczema agents, immunomodulators, anti-dandruff agents, anti-acne agents, anti-seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the anti-psoriatic agents calcipotriol, calcitriol, cholecalciferol, tacalcitol, paricalcitol, alfacalcidol, doxercalciferol, falecalcitriol, roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the antibiotic agents dapsone, dicloxaci I li n, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the anti-fungal agents ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the antiviral agents acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet, docosanol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the anti-inflammatory agents curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the analgesics salicylic acid, ibuprofen, capsaicin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the anti-eczema agents dexpanthenol, corticosteroids, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the immunomodulators pimecrolimus and tacrolimus, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is the antidandruff agent ketoconazole or pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the following anti-acne agents: tretinoin, isotretinoin, adapalene, tazarotene, trifarotene, clascoterone, niacinamide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the anti-seborrheics selenium sulfide, zinc pyrithione, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof. In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the local anesthetics benzocaine, lidocaine, prilocaine, tetracaine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the corticosteroids betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the vitamins vitamin B complex, vitamin C, vitamin D, calcium pantothenate, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of the keratolytic agents citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, sulphur and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, adapalene, a Ifaca Icidol, azelaic acid, benzocaine, betamethasone, calcipotriol, calcitriol, calcium pantothenate, capsaicin, cephalosporin, cholecalciferol, ciclopirox, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, dapsone, deflazacort, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, dicloxacillin, docosanol, doxercalciferol, doxycycline, econazole, erythromycin, falecalcitriol, famciclovir, fluconazole, flunisolide, fluocinolone, foscarnet, fusidic acid, ganciclovir, gentamicin, glycolic acid, hydrocortisone, ibuprofen, indomethacin, isotretinoin, itraconazole, ketoconazole, ketoprofen, lactic acid, lidocaine, loteprednol, metronidazole, miconazole, minocycline, mometasone, mupirocin, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prednisone, prilocaine, quercetin, ribavirin, roflumilast, salicylic acid, selenium sulfide, sulfacetamide sodium, sulphur, taca Icitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, valaciclovir, vidarabine, vitamin B complex, vitamin C, vitamin D, zidovudine, zinc pyrithione, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In one embodiment, the at least one pharmaceutically and/or cosmetically active agent is two active agents selected from the group consisting of calcipotriol and betamethasone, or any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

In a fourth aspect, there is provided a cosmetic use of a composition according to any one of the embodiments of the first or the second aspect. In one embodiment, said cosmetic use is for the non-therapeutic treatment of a condition selected from the group consisting of acne, perioral dermatitis, dandruff, and seborrheic eczema. In one embodiment, said cosmetic use is for the non-therapeutic treatment of acne.

In a fifth aspect, there is provided use of a composition according to any one of the first or second aspects, for delivery of an active agent into dermis and/or epidermis.

In a sixth aspect, there is provided a spraying device comprising the composition as defined in the first aspect and optionally a driving gas.

In a seventh aspect, there is provided a pump device comprising the composition as defined in the first aspect.

In an eighth aspect, there is provided a method for delivering active pharmaceutically and/or cosmetically active agent into the skin. The method comprises the steps of: providing a composition as defined in any one of the embodiments of the first aspect, said composition comprising said at least one active agent; bringing said composition into contact with a skin of a mammal; allowing for penetration of said at least one active agent into dermis and/or epidermis; thereby obtaining said active ingredient within said dermis and/or epidermis. Preferably, the active ingredient is obtained within dermis and/or epidermis in an effective amount, i.e., an amount capable of providing a therapeutic or cosmetic effect in a mammal.

Cosmetic treatment may be treatment of a non-pathological condition of the skin. Cosmetic treatment may be treatment of healthy skin. Typically, cosmetic compositions are sold "over the counter" and do not require any medical prescription or do not require prescription by a medical professional. Provided herein is a non-therapeutic method for delivering a cosmetically active agent into dermis and/or epidermis, comprising the following steps: providing a composition as defined in any one of the embodiments of the first aspect, said composition comprising said at least one active agent; bringing said composition into contact with a skin of a mammal; allowing for penetration of said at least one active agent into dermis and/or epidermis; thereby obtaining said active ingredient within said dermis and/or epidermis.

In a ninth aspect, there is provided a method of treatment of a disease, a disorder or a condition of the dermis and/or epidermis. The method comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a composition as defined in any one of the embodiments of the first aspect. As used herein, the term "excipient" encompasses adjuvants and diluents. The skilled person appreciates that any adjuvants and diluents as disclosed herein are suitable in said pharmaceutical composition and it is withing the knowledge of the skilled person to make the appropriate choice thereof. The skilled person appreciates that the pharmaceutical composition may be adapted to be suitable for the desired administered dose.

It is noted that, as used in this specification and the appended claims, the singular forms "a", "an", and "the" also include plural referents unless the context clearly dictates otherwise. As used herein, when the term "about" or "approximately" is used in relation to a numerical value, it is to be interpreted as a range of ± 10 %, such as ± 9 %, such as ± 8 %, such as ± 7 %, such as ± 6 %, such as ± 5 %, such as ± 4 %, such as ± 3 %, such as ± 2 %, such as ± 1 %. For example, when the value is stated to be about 10, this means that the value is in fact in the range of from 9 to 11, such as in the range of from 9.1 to 10.9, such as in the range of from 9.2 to 10.8, such as in the range of from 9.3 to 10.7, such as in the range of from 9.4 to 10.6, such as in the range of from 9.5 to 10.5, such as in the range of from 9.6 to 10.4, such as in the range of from 9.7 to 10.3, such as in the range of from 9.8 to 10.2, such as in the range of from 9.9 to 10.1.

The skilled person knows that numerical values relating to measurements are subject to measurement errors which place limits on their accuracy. For this reason, the general convention in scientific and technical literature is applied: the last decimal place of a numerical value indicates its degree of accuracy. Where no other error margins are given, the maximum margin is ascertained by applying the rounding-off convention to the last decimal place e.g. for a measurement of 3.5 cm, the error margin is 3.45-3.54. When interpreting ranges of values in patent specifications, the skilled person proceeds on the same basis.

References

FDA Guidance: Topical Dermatologic Corticosteroids, In Vivo Bioequivalence. (1995)

Goon A. T. J., Yosipovitch G., Chan y. H., Goh C. L., "Barrier repair in chronic plaque-type psoriasis", Skin Res Technol (2004), 10, 10-13 Holmback J., Rinwa V., Halthur T., Rinwa P., Carlsson A., Herslof B. "AKVANO®: A Novel Lipid Formulation System for Topical Drug Delivery— In Vitro Studies" Pharmaceutics (2022) 14 (4) 794

Kelchen M. N., Menon G., Ten Eyck P., Prettypaul D., Brogden N. K., "A Pilot Study to Evaluate the Effects of Topically Applied Cosmetic Creams on Epidermal Responses", Skin Pharmacol Physiol (2018), 31, 269-282

Loden M.; Akerstrom U.; Lindahl K.; Berne B., "Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic approach and excised skin penetration", Int. J. Pharm. 2004, 284, 23-30

Queille-Roussel C., Bang B., Clonier F., Lacour J. P., "Enhanced vasoconstrictor potency of the fixed combination calcipotriol plus betamethasone dipropionate in an innovative aerosol foam formulation vs. other corticosteroid psoriasis treatments", Journal of the European Academy of Dermatology and Venereology, 2016, 30, 1951-1956

Runnsjb et al., A Novel Microparticle Based Formulation for Topical Delivery of FOL-005, a Small Peptide (2022) 111 (5), 1309-17)

Simonsen L., Hpy G., Didriksen E., Persson J., Melchior N., Hansen J., "Development of a New Formulation Combining Calcipotriol and Betamethasone Dipropionate in an Ointment Vehicle", Drug Development and Industrial Pharmacy, 30:10, 1095-1102

Uchida T., Kadhum W.R., Kanai S., Todo H., Oshizaka T., Sugibayashi K., "Prediction of skin permeation by chemical compounds using the artificial membrane, Strat-M™", Eur. J. Pharm. Sci. (2015), 67, 113-118. doi: 10.1016/j.ejps.2014.11.002.

Videmont E., Mariani C., Vidal S., Pin D., "Characterization of the canine skin barrier restoration following acute disruption by tape stripping", Veterinary Dermatology (2012), 23, 103-e23 Examples

Example 1: Carriers and compositions of the invention

Materials

Alcohols used in the examples were ethanol 99.9% (EtOH) from VWR International AB, Sweden and 2-propanol (isopropanol or IPA, HPLC grade, Rathburn Chemicals, UK). The silicone oils used in the examples were decamethylcyclopentasiloxane (DMCPS), octamethyltrisiloxane (OMTS) and hexamethyldisiloxane (HMDS) from Dupont, Delaware, USA.

Lipids used in the examples were medium chain monoglycerides (MCM) from Abitec Corporation, Ohio, USA, medium chain triglycerides (MCT) from Alpha Plus AB, Sweden, monoolein, ethyl oleate, almond oil, isopropyl myristate, isopropyl palmitate from Sigma- Aldrich, Germany, and Lipoid S-PC, Lipoid S100, Lipoid S80, Lipoid H100, Lipoid H90 from Lipoid GmbH, Germany.

Calcipotriol was from Cerbios-Pharma SA, Switzerland. All other active and non-active ingredients were from Sigma-Aldrich, Germany.

Methods

The formulation experiments were performed according to the following general procedure. The lipids were weighed and dissolved in ethanol or a mixture of ethanol and other alcohols of the invention. In some experiments complete dissolution of the lipids was promoted by short ultrasonication in a bath-type sonicator at about 30-40 °C or thermomixer (Eppendorf® Thermomixer Compact). Pre-weighed amounts of active agent(s) and additive(s) were added to the vehicle. According to the present invention, the term "vehicle" is synonymous with "carrier". In some experiments the mixture was gently heated and sonicated until a clear solution was formed. The alcoholic solution of lipids was diluted with volatile silicone oil. The thus obtained uncolored or yellow to brownish solutions were stored in air-tight glass vials at room temperature. All carriers and compositions of the invention were single-phase homogeneous liquids at room temperature (20 °C).

The following carriers and compositions (Tables 1 to 5) were used in the present disclosure. Table 1. Basic carrier compositions. (I PA= isopropyl alcohol; IPM=isopropyl myristate;

IPP=lsopropyl palmitate; MCT=medium chain triglycerides; MCM= medium chain monoglycerides; DMCPS= decamethylcyclopentasiloxane; HMDS= hexamethyldisiloxane

Table 2a. Pharmaceutical and cosmetic compositions

Table 2b. Additional pharmaceutical and cosmetic compositions

Table 3. Anti-psoriasis fixed dose combination compositions (% w/w) containing cyclomethicone D5 (DMCPS). BDP= betamethasone dipropionate

Table 4. Anti-psoriasis fixed dose combination compositions (% w/w) containing hexamethyldisiloxane (HMDS).

Table 5. Fixed dose combination compositions for treatment of various conditions (% w/w). Relevant conditions in italic.

Example 2a. In vitro permeation experiments of betamethasone Diffusion cell experiments using artificial membranes have been used widely as a predictive method for simulating permeation through the skin. Earlier studies indicate that an intermediate permeation (flux) is desirable for medications intended for local treatment (Simonsen 2004). A too low flux indicates that the active ingredients do not pass stratum corneum. A too high flux indicates that the active ingredients do pass stratum corneum, but that accumulation of the active ingredients in epidermis and dermis is impaired. What can be considered as intermediate permeation may vary with the specific indication and active ingredient. As a non-limiting example relevant for betamethasone dipropionate in the experimental setup used in this example, a too low flux could be defined as less than 2% of permeation of nominal amount after 24 hours and a too high permeation as more than 15% of nominal amount permeated. The purpose of the experiment was thus to find formulations that give an approximate permeation of the active ingredient between 2% and 15%, which for this compound represent an intermediate permeation.

The diffusion cell system (Holmback et al., 2022; Loden et al., 2004) consisted of a buffer reservoir containing a mixture of PBS buffer (pH 7.4) and ethanol (absolute) 3:1 (v/v), an 8- channel peristaltic pump, eight flow-through diffusion cells (cross section area of 0.5 cm²) placed on a stainless-steel platform which was kept at 37 °C, and an 8-channel fraction collector. The buffer was transported in the system through Teflon tubes (0.5 mm ID). A Strat- M® membrane (Uchida et al., 2015) of appropriate size was placed between the donor chamber and the receiving chamber. The flow rate was adjusted to around 1.5 ml/h. Approximately 5 mg of formulation was applied on top of the membranes. The top of the donor chamber was left open to allow evaporation of the volatile solvent. Fractions of the receptor fluid were collected during the whole period of: 0-2, 2-4, 4-6, 6-10, 10-14, 14-18 and 18-24 hours and filtered with a syringe-filter (Titan, teflon 0.45 pm, 4 mm).

Betamethasone dipropionate concentration in the receptor fluid was analysed using UHPLC (Agilent 1290 Infinity II) coupled to UV DAD detector. 20 pL of undiluted sample was injected using an autosampler at ambient temperature. Elution of the analyte from a Zorbax Eclipse Plus C18 (Agilent) 50 x 2.1 mm, 1.8 pm at 40 °C was followed by detection at 265 nm. The total run time was 12 min, betamethasone dipropionate was eluted at 5.3 min using flow rate 0.3 ml/min with the gradient program shown in Table 6), where mobile phases A was Milli-Q water and mobile phase B was methanol. The concentration of the active compound was calculated from peak areas using a calibration curve based on reference standards, and the accumulated amount of betamethasone dipropionate was calculated. Results are presented in Table 7. Table 6. Gradient program

Time(min) A% B%

0 40 60

3.5 40 60

8.0 0 100

10.0 0 100

10.5 40 60

12 40 60

Table 7. Permeation of BDP through Strat-M membranes for different formulations

Obtained Results and Conclusion

Compositions with higher total lipid contents provided for larger amount of BDP in the receptor fluid. Thus, when present in these compositions, BDP diffused to a larger extent through the artificial membrane. Accordingly, less accumulation in the artificial membrane occurred for the compositions with higher total lipid content.

Example 2b. In vitro permeation experiments of roflumilast

Permeation experiments were also conducted on formulations containing roflumilast. In this case, as a non-limiting example, a too low flux could be defined as less than 2% of permeation of nominal amount after 24 hours. The purpose of this experiment was thus to find formulations that give a permeation of the active ingredient of more than 2% after 24 hours. The same set-up and procedure as in Example 2a was used. Approximately 10 mg of formulation was applied on top of the membranes. Roflumilast concentration in the receptor fluid was analysed using UHPLC (Agilent 1290 Infinity II) coupled to UV DAD detector. 20 pL of undiluted sample was injected using an autosampler at ambient temperature. Elution of the analyte from a Zorbax Eclipse Plus C18 (Agilent) 50 x 2.1 mm, 1.8 pm at 40 °C was followed by detection at 248 nm. The total run time was 14 min, and roflumilast was eluted at 5.6 min using flow rate 0.3 ml/min with the gradient program shown in Table 8, where mobile phases A was Milli-Q water and mobile phase B was methanol. The concentration of the active compound was calculated from peak areas using a calibration curve based on reference standards, and the accumulated amount of roflumilast was calculated. Results are presented in Table 9.

Table 8. Gradient program

Time(min) A% B%

0 65 35

5.0 35 65

11.0 0 100

12.0 0 100

12.1 65 35

14.0 65 35

Table 9. Permeation of roflumilast through Strat-M membranes for different formulations.

* Composition not comprised by the invention ** Composition comprised by the invention

Obtained Results and Conclusion

Compositions comprised within the invention provided for larger amount of roflumilast in the receptor fluid. Thus, when present in these compositions, roflumilast diffused to a larger extent through the artificial membrane.

Example 3: Ex vivo permeation studies with formulations comprising 0.005% calcipotriol and 0.05% betamethasone dipropionate (BDP)

In this example, ex vivo permeation studies using pig skin membranes were performed on five AKVANO® formulations containing 0.005% calcipotriol and 0.05% betamethasone dipropionate (BDP). Accumulation of calcipotriol and BDP was analyzed in both dermis and epidermis by HPLC-MS/MS.

Materials and Methods

The formulations were prepared according to the general description presented in Example 1. Compositions of the five formulations are listed in Table 4.

The preparation of membranes and the ex vivo permeation test was performed as described by Runnsjb et al. The study was performed in two sets of experiments.

A list of the formulations and their composition is given in Table 10.

Preparation of pig skin membranes

Porcine ears were obtained fresh from a local abattoir (Strbmbecks gardsslakt, I llstorp, Sweden). Before use the skin was rinsed with cold running tap water and the inner ear skin was dermatomed (Padgett dermatome model B, Integra Lifesciences, Cincinnati, USA) to a thickness of approximately 500 mm.

Ex vivo permeation tests

Two experiments (Experiment 1 and 2) were performed to analyze permeation of calcipotriol and BDP.

The skin membranes were mounted in a flow-through Bronaugh type diffusion cell equipment. PBS with 0.1% Brij was used as receptor solution. 5 mg of formulation was applied at the start of the experiment. All membranes were randomized and in each experiment all membranes were taken from the same individual pig ear. Skin membranes from different pig individuals were used in experiment 1 and 2. The receptor fluid flow rate was 1.5 ml/h and it was collected for 24 h. Sampling

1. The membranes were washed six times with 0.5 ml PBS buffer.

2. After dismounting, the membranes were gently cleaned with PBS moistured cotton buds.

3. Epidermis was separated from dermis by peeling the membrane and then transferred to a test tube.

4. The cell flange of the dermis part (unexposed skin) was cut with a 10 mm punch and removed.

5. The exposed part was cut into thin strips with a scalpel and transferred to a test tube.

6. 1 ml extraction fluid consisting of methanol: water 50:50 (v/v) was added to the membrane samples.

7. The sample was vortexed and then sonicated for 30 minutes in cold water (2-8°C).

8. The samples were then centrifuged at 14 000 rpm and transferred to HPLC vials.

Analysis ofcalcipotriol and BDP

The samples were analysed using reversed phase LC-MS/MS. The MS instrument (Quattro Micro triple quadrupole mass spectrometer (Waters, Altrincham, Cheshire, UK) was used in the electrospray-mode monitoring positive ions (ESI+). The capillary voltage was 5.0 kV, the temperature of the ion source was 130°C, and the desolvation temperature was 350°C. Collision- induced dissociation was performed using argon as collision gas and the pressure of the collision cell was 3 x 10“³ mbar. For quantification, multiple-reaction monitoring (MRM) was performed: Calcipotriol (m/z 395->150.5), BDP (m/z 504.6^278.5). The monitored ions were all individually optimized.

The MS instrument was connected to LC pumps (Shimadzu LC10ADVP, Shimadzu Inc., Kyoto, Japan). Isocratic elution was performed 80/20 0.5% Formic acid/acetonitrile for 4 minutes after injection, then gradient elution to 40/60 over 2 min followed by another isocratic elution step for 6 min. Partially filled loop injections of 10 pl in a 20 pl loop volume containing 10 pl of water as a focus liquid were made with a CTC-pal autosampler (CTC Analytics AG, Zwingen, Switzerland). The flow rate was 0.15 ml/min, and the LC column was an Ascentis Express 90 A F5, 15cm x 2.1 mm, 2.7pm (Supelco, PA, US).

Stock solutions (1 mg/ml) of Calcipotriol hydrate (CH) (Sigma Aldrich, Sweden) and Betamethasone Dipropionate (BDP) (Sigma Aldrich, Sweden) were prepared in methanol. Calibration standards were prepared by dilution of the stock solutions in extraction and receptor buffers, in the range of 0.5-100 ng/ml.

Obtained Results and Conclusion

Permeation ofcalcipotriol and betamethasone dipropionate

Concentrations of calcipotriol and BDP were below detection limit in all samples of receptor fluid.

Calcipotriol and betamethasone dipropionate in epidermis and dermis

Results are presented in Table 10. As can be seen in the table, a larger amount of calcipotriol and BDP was accumulated in epidermis and dermis (underlying the stratum corneum) when inventive compositions were used.

Table 10. Amount of calcipotriol and betamethasone dipropionate accumulated in epidermis and dermis for different formulations after 24 hours (Mean)

* Composition not comprised by the invention ** Composition comprised by the invention Example 4a: Skin blanching studies with AKVANO® formulations containing 0.005% calcipotriol and 0.05% betamethasone di propionate

Topical corticosteroid potency can be assessed using the vasoconstriction assay, which evaluates the blanching (whitening) response of healthy skin induced by a topical corticosteroid (e.g. betamethasone).

Since the blanching response is due to vasoconstriction elicited by the diffusion of corticosteroid across stratum corneum, the intensity of blanching is related to the availability of the active compound to capillary blood vessels in dermis underlying the stratum corneum and the potency of the applied corticosteroid.

The skin blanching technique has been recommended for ranking the potency of topical corticosteroids based on its correlation with clinical efficacy in patients with psoriasis and is also used in bioequivalence studies, since it could be anticipated to reflect the efficacy of delivering the active substance to the relevant skin layer (FDA Guidance 1995). The purpose of this experiment was to evaluate the diffusion of betamethasone across stratum corneum into the skin and the subsequent vasoconstriction effect.

Skin color measurements were used to study the vasoconstriction effect of betamethasone dipropionate in the skin. 2.5 cm² circular test areas were marked on the skin of the volar forearms of a male subject. Two areas on each arm were prepared for each formulation. Two baseline measurements of skin color were done (with 20 minutes delay between) by using DSM Colormeter (Cortex Technology, Denmark) which is based on an active color detecting chip where illumination is provided by white LEDs. The measured quantity, the a* parameter in the CIE 1976 (L*, a*, b*) color space, is considered to give a representative scale of the blanching effect (Queille-Roussel 2016). Quadruplicate measurements were done on each test area. 15 mg of each formulation was then applied to the test areas (6 mg/cm²), whereafter they were covered with 18 mm Finn Chamber polypropylene coated chambers. After 2 hours the chambers were removed, and the test areas gently swabbed by a damp paper wipe to remove excessive formulation. After 5 minutes, the skin color was measured again and then hourly for 12 hours. The reduction of a* from the baseline to the measured a*, Aa*, is used as response and AUC(12 h) is calculated. Results from the skin blanching experiments are presented in Table 11. Since the absolute blanching effect varies between experiments due to air temperature, sun exposure, physical activities and other factors, the results were congregated by normalizing to a reference formulation in each experiment and pooling the results in one table. Table 11. Skin blanching of different formulations containing calcipotriol and betamethasone dipropionate

* Composition not comprised by the invention ** Composition comprised by the invention Conclusion

Formulations comprised by the invention give a stronger skin blanching effect than formulations not comprised by the invention, indicating that delivery of the active ingredient is more effective for these formulations. Example 4b: Skin blanching studies with AKVANO® formulations containing 0.1% mometasone furoate

In a second skin blanching experiment the vasoconstriction effect of mometasone furoate was studied. 2.5 cm² circular test areas were marked on the skin of the volar forearms of a male subject. Two areas on each arm were prepared for each formulation. Two baseline measurements of skin color were done (with 20 minutes delay between) by using Dermalab instrument (Cortex Technology, Denmark) equipped with a colorimeter probe, which is based om the same principle as the Colormeter used in Experiment 4a. Quadruplicate measurements were done on each test area. 10 mg of each formulation was then applied to the test areas (4 mg/cm²), whereafter they were covered with 18 mm Finn Chamber polypropylene coated chambers. After 2 hours the chambers were removed, and the test areas gently swabbed by a damp paper wipe to remove excessive formulation. After 5 minutes, the skin color was measured again and then hourly for 12 hours. The reduction of a* from the baseline to the measured a*, Aa*, is used as response and AUC(12 h) is calculated. Results from the skin blanching experiments are presented in Table 12. In this case the formulation giving the highest AUC(12 h) was used for normalization.

Table 12. Skin blanching of different formulations containing mometasone furoate

Formulations comprised by the invention give a stronger skin blanching effect than formulations not comprised by the invention, indicating that delivery of the active ingredient is more effective for these formulations. Example 5: Stability studies

In order to ensure usefulness of the compounds of the invention, a four-month stability study of formulations comprising calcipotriol and betamethasone was performed (for compositions, see Table 4). Method of Analysis

Calcipotriol and betamethasone dipropionate stability analysis was performed using UHPLC (Agilent 1290 Infinity II) coupled to UV DAD detector. 1 pL of undiluted sample was injected using an autosampler at ambient temperature. Separation of the two analytes with an InfinityLab Poroshell 120 EC-C18 column (Agilent, 100x2.1 mm, particle size 1.9 pm) at 40 °C was followed by detection at 265 nm. The total run time was 35 min, betamethasone dipropionate was eluted at 12 min and calcipotriol at 19 min using flow rate 0.3 ml/min with the gradient program shown in Table 13), where mobile phases A was 0.16% acetic acid and 0.16% triethyl amine in MilliQ. water and mobile phase B was 0.16% acetic acid and 0.16% triethyl amine in methanol. The concentrations of the active compounds were calculated from peak areas using a calibration curve based on reference standards. Results are presented in Table 14. Table 13. Gradient program

Time(min) A% B%

0 40 60

15 40 60

20 0 100

25 0 100

26 40 60

35 40 60

Table 14. Four months stability study. The values shown represent the percentage of assay (calcipotriol and betamethasone dipropionate) against nominal after 4 months in 40 °C.

Conclusion

Both studied formulations show a good chemical stability after 4 months under accelerated conditions.

Example 6: Skin barrier recovery

Diseases affecting the skin are often associated with a negative impact on the skin barrier function (Goon 2004). It is therefore desired that topical medications for treatment of skin disorders can assist in the recovery of the skin barrier, either through the active ingredient itself or through the components of the vehicle. Trans-epidermal water loss (TEWL), erythema index (E. I .) and capacitance (hydration) are considered to be parameters reflecting the skin barrier homeostasis (Videmont 2012, Kelchen 2018).

With the intention to investigate the potential effects on the barrier function, two vehicles, AC- 126 and AC-129, were tested with respect to these three variables on a healthy male person. E.L was measured using a DSM II Colormeter (Cortex, Denmark), while a Dermalab equipment (Cortex, Denmark) was used for measuring TEWL (open chamber probe) and capacitance.

Four quadratic areas of 5.5 x 5.5 cm were marked on each volar forearm with a pen and measured for baseline. 3.8 x 3.8 cm pieces of adhesive tape (38 mm Strong Transparent tesaPack, Tesa, Germany) were applied to the central part of each test area, gently compressed with a finger, and swiftly removed after 30 seconds. The stripping procedure was repeated 20 times.

With the help of a transparent plastic foil mask with a 3.5 x 3.5 cm opening, the test solutions were then sprayed (approximately 4 mg/cm²) onto the test areas, except for two untreated control areas. Measurements in quadruplicates of each test area, immediately followed by new applications of test formulations, were done twice daily for three days.

The skin stripping resulted in an increase of all three parameters studied and continued to increase for several hours after application of the test compositions. Therefore, the maximum value during the first day (A_max) was chosen as a measurement of the barrier disruption effect. The recovery rate (Arecovery) was determined as (A₃ da_ys - A_max)/(A_max- Abaseiine), where A₃ days is the measurement after 3 days and Abaseiine is the measurement before tape stripping.

Results and conclusion

The results are presented in Table 15 and show a better average recovery rate for vehicle AC- 129 (comprised by the invention) compared to both AC-126 (not comprised by the invention) and untreated control in respect of all three parameters. Table 15. Recovery of skin barrier. Change in erythema index, trans-epidermal water loss and capacitance 3 days after skin stripping, relative to maximum value Day 1 (mean values)

Example 7: Permeation ofcurcumin through stratum corneum

The permeation of active ingredients through stratum corneum can be evaluated by measuring the coloring effect of for instance curcumin on different skin layers. By measuring the color before and after stripping the skin a certain number of times, it is possible to evaluate the proportion of applied curcumin that has diffused through the outermost layer of stratum corneum.

3 mg of curcumin was added to 1 g each of vehicles AC-133, AC-134, AC-135 and AC-136 . The mixture was gently heated to about 40 °C and stirred vigorously for 5 minutes, and then allowed to cool. Since all curcumin substance had not been dissolved in any of the vehicles, the mixtures were left to equilibrate overnight. Undissolved particles settled on the bottom of the vial, so samples of the saturated supernatant could be taken.

1. Circular test areas of 3.1 cm² were marked on the skin of the volar forearms of a male subject.

2. Baseline measurement of skin color was done by using Dermalab (Cortex Technology, Denmark) equipped with a colormeter probe; the same instrument as in Experiment 4b. The measured quantity, the b* parameter in the CIE 1976 (L *, a*, b*) color space, have previously been found to have a linear relationship with the amount of curcumin absorbed by the skin.

3. 8 pl of each of the four curcumin formulations in Table 16 were applied to the test areas.

4. 15 minutes after application the test area was gently swabbed by a damp paper towel to remove excessive formulation.

5. The skin color was measured a second time.

6. After the measurement, each test area was stripped with transparent adhesive tape ten times.

7. Color intensity was measured a third time.

8. The relative amount of curcumin in the skin was calculated as the difference between the measured b* and the baseline (Ab*) after ten tape strippings, divided by the difference measured before stripping.

The numbers shown in Table 16 are average values from sixteen replicate measurements (quadruplicate measurements on four test areas) for each treatment and occasion.

Table 16. Average ratios of curcumin in stripped skin after application of saturated solutions in different vehicles

Conclusion

Formulations comprised by the invention give a deeper permeation than formulations not comprised by the invention, indicating that delivery of the active ingredient is more effective for these formulations.

Claims

1. A topical composition comprising a carrier, which carrier comprises at least two lipids selected from the group consisting of: a phospholipid; a monoglyceride; and a fully acylated ester of C1-C3 alcohol; wherein said phospholipid is present in an amount of from about 1.5 to about 7.5 % by weight of the carrier, said monoglyceride is present in amount of from about 1.5 to about 7.5 % by weight of the carrier, said fully acylated ester of C1-C3 alcohol is present in an amount of from about 1.5 to about 5 % by weight of the carrier, and wherein the total lipid content is from about 3.0 % to about 15 % by weight of the carrier; and a volatile solvent selected from the group consisting of: ethanol and volatile silicone oil; C3-C4 alcohol and volatile silicone oil and ethanol; and C3-C4 alcohol and volatile silicone oil; and wherein the composition further comprises at least one pharmaceutically and/or cosmetically active agent selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, antiinflammatory agents, analgesics, anti-eczema agents, immunomodulators, anti-dandruff agents, anti-acne agents, anti-seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents.

2. Composition according to claim 1, wherein said at least two lipids are three lipids.

3. Composition according to any one of the preceding claims, wherein said total lipid content is from about 5.0 to about 14.0 % by weight, such as from about 5.0 to about 13.0 % by weight, such as from about 6.0 % to about 12.0 % by weight.

4. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.5 % to about 6.0 % by weight of phospholipid.

5. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.5 % to about 6.0 % by weight of monoglyceride.

6. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

7. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.5 % to about 6.0 % by weight of phospholipid, from about 1.5 % to about 6.0 % by weight of monoglyceride, and from about 1.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

8. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.8 % to about 5.0 % by weight of phospholipid.

9. Composition according to any one of the preceding claims, wherein the carrier comprises from about 2.0 % to about 5.5 % by weight of monoglyceride.

10. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.5 % to about 2.5 % by weight of fully acylated ester of C1-C3 alcohol.

11. Composition according to any one of the preceding claims, wherein the carrier comprises from about 1.8 % to about 5.0 % by weight of phospholipid, from about 2.0 % to about 5.5 % by weight of monoglyceride, and from about 1.5 % to about 2.5 % by weight of fully acylated ester of C1-C3 alcohol.

12. Composition according to any one of claims 1-6, wherein the carrier comprises from about 2.5 % to about 6.0 % by weight of phospholipid, from about 2.5 % to about 6.0 % by weight of monoglyceride, and from about 2.5 % to about 4.5 % by weight of fully acylated ester of C1-C3 alcohol.

13. The composition according to any one of the preceding claims, wherein said solvent is present in an amount of from about 70 % to about 97 %, or such as from about 75 % to about 96 %, or such as from about 80 % to about 95 %, or such as from about 85 % to about 93 % by weight of the carrier.

14. Composition according to any one of the preceding claims, wherein said silicone oil is present in an amount of at least 15 %, such as at least 17 %, such as at least 20 %, such as at least 22 %, such as at least 25 %, such as at least 27 %, such as at least 20 %, such as at least 32 %, such as at least 35 %, such as by 37 %, such as at least 40 %, such as at least 42 %, such as at least 45 %, such as at least 50 %, such as at least 52 % by weight of the carrier.

15. Composition according to any one of claims 1-12, wherein said silicone oil is present in an amount of at least 55 %, such as by 60 %, such as by 61 %, such as by 62 %, such as by 65 %, such as at least 68 %, such as at least 70 %, such as at least 75 %, such as at least 80 %, or such as at least 85 % by weight of the carrier.

16. The composition according to any one of claims 1-13, wherein said silicone oil is present in an amount of from about 10 % to about 90 %, such as from about 15 % to about 85 %, or such as from about 15 % to about 75 % by weight of the carrier.

17. The composition according to any one the of claims 1-13, wherein said silicone oil is present in an amount of from about 60 % to about 95 %, such as from about 60 % to about 90 %, or such as from about 60 % to about 80 %, or such as from about 65 % to about 80 %, or such as from about 68 % to about 78 %, or such as from about 65 % to about 75 % by weight of the carrier.

18. Composition according to any one of the preceding claims, wherein said silicone oil has a boiling point of 200 °C or less, such as of 190 °C or less, such 180 °C or less, such as 170 °C or less, such as 160 °C or less, such as 150 °C or less, such 140 °C or less, such as 130 °C or less, such as 120 °C or less, such as 110 °C or less, such as from about 98 °C to about 101 °C.

19. Composition according to any one of the preceding claims, wherein said silicone oil has a boiling point of from about 50 °C to about 200 °C, such as from about 60 °C to about 160 °C, such as from about 70 °C to about 150 °C, such as from about 80 °C to about 130 °C, such as from about 90 °C to about 110 °C, such as from about 95 °C to about 105 °C, such as from about 98 to about 101 °C.

20. The composition according to any one of the preceding claims, wherein said silicone oil is selected from the group consisting of cyclic or straight chain silicone oils with up to six siloxane units.

21. The composition according to any one of claims 1-19, wherein said silicone oil is selected from the group consisting of decamethylcyclopentasiloxane, decamethyltetrasiloxane, hexamethyldisiloxane and octamethyltrisiloxane.

22. The composition according to any one of claims 1-17 and 21, wherein said silicone oil is decamethyltetrasiloxane, or hexamethyldisiloxane or octamethyltrisiloxane.

23. The composition according to any one of the preceding claims, wherein said ethanol is present in an amount of from about 15 % to about 75 %, such as from about 20 % to about 70 %, such as from about 30 % to about 75 %, such as from about 40 % to about 70 %, such as from about 45 % to about 68% by weight of the carrier; or from about 5 % to about 50 %, such as from about 5 % to about 40 %, such as from about 10 % to about 30 %, such as from about 12 % to about 25 %, such as from about 15 % to about 23 % by weight of the carrier.

24. The composition according to any one of the preceding claims, wherein said ethanol is present in an amount of at most 30 %, such as at most 25 %, such as at most 20 %, such as at most 15 % by weight of the carrier.

25. Composition according to any one of the preceding claims, wherein said C3-C4 alcohol is selected from the group consisting of n-propanol, isopropanol, propylene glycol, and mixtures thereof.

26. Composition according to any one of the preceding claims, wherein said C3-C4 alcohol is present in an amount of from about 5 % to about 50 %, such as from about 5 % to about 40 %, such as from about 10 % to about 30 %, such as from about 12 % to about 25 %, such as from about 15 % to about 23 % by weight of the carrier.

27. Composition according to any one of the preceding claims, wherein said ethanol and said C3-C4 alcohol are present in a ratio of at least 1:10, such as at least 2:10, such as at least 3:10, such as at least 4:10, such as at least 5:10, such as at least 6:10, such as at least 7:10, such as at least 8:10, such as at least 9:10, or such as about 1:1, of ethanol: C3-C4 alcohol.

28. Composition according to any one of claims 1-26, wherein said C3-C4 alcohol and said ethanol are present in a ratio of at least 1:10, such as at least 2:10, such as at least 3:10, such as at least 4:10, such as at least 5:10, such as at least 6:10, such as at least 7:10, such as at least 8:10, such as at least 9:10, or such as about 1:1, of C3-C4 alcohol: ethanol.

29. The composition according to any one of the preceding claims, wherein said monoglyceride is selected from the group consisting of monoolein and medium chain monoglycerides optionally comprising at least one Cs-Cio monoacylglycerol, wherein said at least one Cs-Cio monoacylglycerol and/or said monoolein comprise at least 40 % by weight of said medium chain monoglycerides.

30. The composition according to claim 29, wherein said monoolein comprises at least 50 % by weight of monooleoylglycerol.

31. The composition according to any one of claims 29-30, wherein said medium chain monoglycerides comprises at least one monoacylglycerol selected from the group consisting of Cs-monoacylglycerol, Cio-monoacylglycerol, and a combination thereof.

32. The composition according to any one the preceding claims, wherein said phospholipid comprises at least 45 % of phosphatidylcholine; such as at least 50 % of phosphatidylcholine; such as at least 55 % of phosphatidylcholine; such as at least 60 % of phosphatidylcholine; such as at least 65 % of phosphatidylcholine; such as at least 70 % of phosphatidylcholine; such as at least 75 % of phosphatidylcholine; such as at least 80 % of phosphatidylcholine; such as at least 85 % of phosphatidylcholine; such as at least 90 % of phosphatidylcholine; such as at least 93 % of phosphatidylcholine; such as at least 95 % of phosphatidylcholine; or such as at least 97 % by weight of phosphatidylcholine.

33. The composition according to any one of the preceding claims, wherein said phospholipid comprises or essentially consists of phosphatidylcholine.

34. The composition according to any one of claims 32-33, wherein said phosphatidylcholine is natural phosphatidylcholine or synthetic phosphatidylcholine.

35. The composition according to any one of claims 32-34, wherein said phosphatidylcholine is selected from the group consisting of phosphatidylcholine from soybeans, phosphatidylcholine from sunflower seeds, and phosphatidylcholine from rapeseed; such as the group consisting of phosphatidylcholine from soybeans, and phosphatidylcholine from sunflower seeds; or such as wherein said phosphatidylcholine is phosphatidylcholine from soybeans.

36. The composition according to any one the preceding claims, wherein said phospholipid is selected from the group consisting of Lipoid S PC, Lipoid S 100, Lipoid S 80, Lipoid S 75, Lipoid P 75, Lipoid P 100, Lipoid H 90 and Lipoid H 100; such as the group consisting of Lipoid S 100, Lipoid S 80, and Lipoid H 100; such as wherein said phospholipid is Lipoid S 100.

37. The composition according to claim 34, wherein said synthetic phosphatidylcholine is selected from the group consisting of dimyristoyl phosphatidylcholine and dioleoyl phosphatidylcholine.

38. The composition according to any one of the preceding claims, wherein said fully acylated ester of C1-C3 alcohol is an acyl ester of methanol, ethanol, n-propanol or isopropanol; or is a diacyl ester of ethylene glycol or propylene glycol; or is a triacyl ester of glycerol.

39. The composition according to any one of the preceding claims, wherein an acyl group of said fully acylated ester of C1-C3 alcohol comprises Ce-Cis saturated or monounsaturated fatty acids.

40. The composition according to any one of the preceding claims, wherein said fully acylated ester of C1-C3 alcohol is selected from the group consisting of isopropyl myristate, ethyl oleate, medium chain triglycerides, and almond oil; and preferably is isopropyl myristate.

41. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of anti-psoriatic agents, such as vitamin D analogs like calcipotriol, calcitriol, cholecalciferol, tacalcitol, paricalcitol, alfacalcidol, doxercalciferol, falecalcitriol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof and other anti-psoriatic agents such as roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antibiotic agents, such as dapsone, dicloxacillin, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-fungal agents, such as ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antiviral agents, such as acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet and docosanol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-inflammatory agents, such as curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; analgesics, such as salicylic acid, ibuprofen, capsaicin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-eczema agent, s such as dexpanthenol, corticosteroids, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; calcineurin inhibitors/immunomodulators, such as pimecrolimus and tacrolimus, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-dandruff agents ,such as ketoconazole and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-acne agents, such as retinoids like tretinoin, isotretinoin, adapalene, tazarotene, trifarotene, and other agents like clascoterone, niacinamide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-seborrheics, such as selenium sulfide, zinc pyrithione, and salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; local anesthetics, such as benzocaine, lidocaine, prilocaine, tetracaine and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; corticosteroids, such as betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; vitamins, such as vitamin B complex, vitamin C, vitamin D, calcium pantothenate, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; and keratolytic agents, such as citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, sulphur and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

42. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, adapalene, alfacalcidol, azelaic acid, benzocaine, betamethasone, calcipotriol, calcitriol, calcium pantothenate, capsaicin, cephalosporin, cholecalciferol, ciclopirox, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, dapsone, deflazacort, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, dicloxaci Ilin, docosanol, doxercalciferol, doxycycline, econazole, erythromycin, fa leca Icitriol, famciclovir, fluconazole, flunisolide, fluocinolone, foscarnet, fusidic acid, ganciclovir, gentamicin, glycolic acid, hydrocortisone, ibuprofen, indomethacin, isotretinoin, itraconazole, ketoconazole, ketoprofen, lactic acid, lidocaine, loteprednol, metronidazole, miconazole, minocycline, mometasone, mupirocin, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prednisone, prilocaine, quercetin, ribavirin, roflumilast, salicylic acid, selenium sulfide, sulfacetamide sodium, sulphur, tacalcitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, valaciclovir, vidarabine, vitamin B complex, vitamin C, vitamin D, zidovudine, zinc pyrithione, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

43. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, alfacalcidol, betamethasone, calcipotriol, calcitriol, capsaicin, cholecalciferol, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, docosanol, doxercalciferol, econazole, erythromycin, fa leca Icitriol, flunisolide, fusidic acid, hydrocortisone, ibuprofen, indomethacin, ketoconazole, ketoprofen, lactic acid, lidocaine, metronidazole, miconazole, minocycline, mometasone, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prilocaine, ribavirin, roflumilast, salicylic acid, selenium sulfide, tacalcitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, vitamin C, vitamin D, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

44. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent has a log K_ow value within a range of 1-8, such as within a range of 2-5; or within a range of -2-7, such as within a range of -1.8-5.

45. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is at least two active agents.

46. The composition according to claim 45, wherein said at least two active agents are selected from the group consisting of calcipotriol and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of tazarotene and mometasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of roflumilast and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; the group consisting of trifarotene and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; the group consisting of tacrolimus and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of capsaicin and lidocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of hydrocortisone and minocycline and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of trifarotene and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of dexpanthenol and urea and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of lidocaine and prilocaine and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of hydrocortisone and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of ketoconazole and betamethasone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of clindamycin and salicylic acid and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; or the group consisting of fusidic acid and hydrocortisone and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

47. The composition according to any one of claims 45-46, wherein said at least two active agents are selected from the group consisting of calcipotriol and betamethasone, tazarotene and mometasone furoate, roflumilast and hydrocortisone, trifarotene and minocycline, tacrolimus and lidocaine, capsaicin and lidocaine, lidocaine and prilocaine, or any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

48. The composition according to any one of claims 45-47, wherein said at least two active agents are calcipotriol and betamethasone, or any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

49. The composition according to claim 48, wherein betamethasone and calcipotriol are present in a ratio of at least 4:1, such as at least 5:1, such as at least 6:1, such as at least 7:1, such as at least 8:1, such as at least 9:1, such as at least 10:1, such as at least 20:1.

50. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.001 % to about 20 %, such as from about 0.02 % to about 15 %, such as from about 0.05 % to about 10 %, such as from about 0.05 % to about 5 %, such as from about 0.05 % to about 3 %, or such as from about 0.05 % to about 1 % by weight of the composition.

51. The composition according to any one of the preceding claims, wherein said at least one pharmaceutically and/or cosmetically active agent is present in an amount of from about 0.002 % to about 0.01 %, or from about 0.01 % to about 0.05 %, or from about 0.05 % to about

0.20 %, or from about 0.20 % to about 0.25 %, or from about 0.25 % to about 0.30 %, or about 0.5 %, or about 1.0 %, or from about 1.0 % to about 1.4 %, or from about 1.8 % to about 1.9 %, or about 2.0 %, or from about 2.0 % to about 2.6 %, or about 3.0 %, or about 5.0 %, or about 8.0 %, or about 10.0 %, or about 15.0 %, or about 20.0 % by weight of the composition.

52. The composition according to any one of the preceding claims, further comprising water in an amount of at maximum 2 % by weight of the carrier, such as at maximum 1 % by weight of the carrier, such as at maximum 0.5 % by weight of the carrier.

53. The composition according to any one of the preceding claims, wherein said carrier is essentially water free.

54. The composition according to any one of the preceding claims, further comprising at least one excipient.

55. The composition according to claim 54, wherein said excipient is selected from the group consisting of lactic acid, triethanolamine, oleic acid, triisopropanolamine and malic acid.

56. The composition according to any one of claims any one of the preceding claims, further comprising a pH modulator; such as an acidifying agent, an alkalizing agent and/or a buffering agent; optionally wherein said pH modulator is present in an amount of from about 0.1 % to about 20 %, such as from about 0.2 % to about 5 %, such as from about 1 % to about 4 %, such as from about 2 % to about 3 %; or such as from about 5 % to about 20 %, such as from about 5 % to about 15 %, such as from about 5 % to about 11 % by weight of the carrier.

57. The composition according to claim 56, wherein said pH modulator is selected from the group consisting of lactic acid, citric acid, glycolic acid, acetic acid, triethanolamine, oleic acid, triisopropanolamine, and malic acid.

58. The composition according to any one of claims 56-57, wherein said pH modulator is lactic acid.

59. The composition according to any one of the preceding claims, further comprising at least one keratolytic agent, optionally wherein said keratolytic agent is present in an amount of from about 0.5 % to about 10 %, such as from about 1 % to about 5 %, such as from about 1 % to about 3 %, such as from about 3 % to about 5 %; or such as from about 5 % to about 8 % by weight of the carrier.

60. The composition according to claim 58, wherein said keratolytic agent is selected from the group consisting of glycolic acid, lactic acid, malic acid, salicylic acid, allantoin, urea, and sulphur.

61. The composition according to any one of claims 59-60, wherein said keratolytic agent is lactic acid.

62. The composition according to any one the preceding claims, wherein said carrier is a singlephased homogeneous liquid at room temperature (20 °C).

63. The composition according to any one the preceding claims, wherein said carrier and/or said composition is stable at room temperature (20 °C) at room temperature, for an extended period of time, such as for at least 1 day, such as for at least 1 week, such as for at least 2 weeks, such as for at least 5 weeks, such as for at least 10 weeks, such as for at least 15 weeks, such as for at least 20 weeks, such as for at least 25 weeks, such as for at least 30 weeks, such as for at least 40 weeks, such as for at least 50 weeks, such as for at least 1 years, such as for at least 1.5 years, such as for at least 2 years, such as for at least 3 years, such as for at least 4 years, such as for at least 5 years.

64. The composition according to any one of the preceding claims, for administration in the form of a spray, a drop or a solution.

65. The composition according to any one of the preceding claims, further comprising a cosolvent.

66. The composition according to claim 65, wherein said co-solvent is selected from the group consisting of propylene glycol, oleic acid, glycerol, polyethylene glycol and diethylene glycol monoethyl ether; such as the group consisting of propylene glycol, oleic acid and glycerol.

67. The composition according to any one of claims 65-66, wherein said co-solvent is present in an amount of at most 20 %, such as at most 15 %, such as at most 10 %, such as at most 5 % by weight of the carrier.

68. The composition according to any one of the preceding claims, further comprising an antioxidant.

69. The composition according to claim 68, wherein said antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate and propyl gallate, thiols, ascorbic acid, - polyphenols, tocopherols, tocotrienols, EDTA, phosphonates, acetic acid, citric acid, glycolic acid, lactic acid, and any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof, such as the group consisting of alpha-tocopherol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate, and propyl gallate.

70. The composition according to any one of the preceding claims, wherein said active agent is capable of permeation through stratum corneum.

71. The composition according to claim 70, wherein said active agent is capable of permeation into epidermis and/or dermis, such as permeation into one or more of stratum lucideum, stratum granulosum, stratum spinosum and stratum basale and/or dermis.

72. A cutaneous composition comprising a carrier, which carrier comprises at least two lipids selected from the group consisting of: a phospholipid; a monoglyceride; and a fully acylated ester of C1-C3 alcohol; wherein said phospholipid is present in an amount of from about 1.5 to about 7.5 % by weight of the carrier, said monoglyceride is present in amount of from about 1.5 to about 7.5 % by weight of the carrier, said fully acylated ester of C1-C3 alcohol is present in an amount of from about 1.5 to about 5 % by weight of the carrier, and wherein the total lipid content is from about 3.0 % to about 15 % by weight of the carrier; and a volatile solvent selected from the group consisting of: ethanol and volatile silicone oil;

C3-C4 alcohol and volatile silicone oil and ethanol; and C3-C4 alcohol and volatile silicone oil; and wherein the composition further comprises at least one pharmaceutically and/or cosmetically active agent selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, antiinflammatory agents, analgesics, anti-eczema agents, immunomodulators, anti-dandruff agents, anti-acne agents, anti-seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents, wherein said carrier is suitable for delivering said active agent through stratum corneum.

73. The composition according to claim 72, wherein said carrier is as defined in any one of claims 1 to 71.

74. Composition according to any one of claims 1-71 for use in the treatment of a disease, a disorder or a condition of the skin.

75. Composition for use according claim 74, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of anti-psoriatic agents, antibiotic agents, anti-fungal agents, antiviral agents, anti-inflammatory agents, analgesics, anti-eczema agents, immunomodulators, anti-dandruff agents, anti-acne agents, anti- seborrheics, local anesthetics, corticosteroids, vitamins, and keratolytic agents.

76. Composition for use according to any one of claims 74-75, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of anti-psoriatic agents, such as calcipotriol, calcitriol, cholecalciferol, taca Icitol, pa rica Icitol, a Ifaca Icidol, doxercalciferol, fa leca Icitriol, roflumilast, tapinarof, tazarotene, tretinoin, betamethasone, mometasone, clobetasol and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antibiotic agents such as dapsone, dicloxaci Ilin, doxycycline, cephalosporin, erythromycin, gentamicin, metronidazole, minocycline, fusidic acid, mupirocin, clindamycin, erythromycin, salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-fungal agents, such as ciclopirox, clotrimazole, econazole, itraconazole, fluconazole, ketoconazole, metronidazole miconazole, terbinafine, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; antiviral agents such as acyclovir, famciclovir, ganciclovir, penciclovir, ribavirin, vidarabine, zidovudine, valaciclovir, foscarnet and docosanol, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-inflammatory agents such as curcumin, diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, quercetin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; analgesics such as salicylic acid, ibuprofen, capsaicin, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-eczema agents, such as dexpanthenol, corticosteroids, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; calcineurin inhibitors/immunomodulators such as pimecrolimus and tacrolimus, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-dandruff agents such as ketoconazole and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-acne agents, such as retinoids like tretinoin, isotretinoin, adapalene, tazarotene, trifarotene, and other agents like clascoterone, niacinamide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; anti-seborrheics, such as selenium sulfide, zinc pyrithione, and salicylic acid, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; local anesthetics such as benzocaine, lidocaine, prilocaine, tetracaine and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; corticosteroids such as betamethasone, clobetasol, cortisone, corticosterone, deflazacort, desonide, desoximethasone, dexamethasone, prednisone, flunisolide, fluocinolone, hydrocortisone, loteprednol, mometasone, triamcinolone acetonide, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; vitamins, such as vitamin B complex, vitamin C, vitamin D, calcium pantothenate, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof; keratolytic agents, such as citric acid, glycolic acid, lactic acid, salicylic acid, sulfacetamide sodium, urea, sulphur and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

77. Composition for use according to any one of claims 74-76, wherein said at least one pharmaceutically and/or cosmetically active agent is selected from the group consisting of acyclovir, adapalene, alfacalcidol, azelaic acid, benzocaine, betamethasone, calcipotriol, calcitriol, calcium pantothenate, capsaicin, cephalosporin, cholecalciferol, ciclopirox, citric acid, clascoterone, clindamycin, clobetasol, clotrimazole, corticosterone, cortisone, curcumin, dapsone, deflazacort, desonide, desoximethasone, dexamethasone, dexpanthenol, diclofenac, dicloxacillin, docosanol, doxercalciferol, doxycycline, econazole, erythromycin, falecalcitriol, famciclovir, fluconazole, flunisolide, fluocinolone, foscarnet, fusidic acid, ganciclovir, gentamicin, glycolic acid, hydrocortisone, ibuprofen, indomethacin, isotretinoin, itraconazole, ketoconazole, ketoprofen, lactic acid, lidocaine, loteprednol, metronidazole, miconazole, minocycline, mometasone, mupirocin, naproxen, niacinamide, paricalcitol, penciclovir, pimecrolimus, prednisone, prilocaine, quercetin, ribavirin, roflumilast, salicylic acid, selenium sulfide, sulfacetamide sodium, sulphur, tacalcitol, tacrolimus, tapinarof, tazarotene, terbinafine, tetracaine, tretinoin, triamcinolone acetonide, trifarotene, urea, valaciclovir, vidarabine, vitamin B complex, vitamin C, vitamin D, zidovudine, zinc pyrithione, and pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

78. Composition for use according to any one of claims 74-77, wherein said at least one pharmaceutically and/or cosmetically active agent is two active agents selected from the group consisting of calcipotriol and betamethasone, or any pharmaceutically and/or cosmetically acceptable salts and derivatives thereof.

79. Cosmetical use of a composition according to any one of claims 1-71 for the non- therapeutic treatment of a condition selected from the group consisting of acne, perioral dermatitis, dandruff, seborrheic eczema; such as wherein said condition is acne.

80. Use of a composition as defined in any one of claims 1-71 for delivery of an active agent into dermis and/or epidermis.

81. Spraying device comprising the composition as defined in any one of claims 1-71 and optionally a driving gas.

82. A method for delivering a pharmaceutically and/or cosmetically active agent into dermis and/or epidermis, the method comprising: providing a composition as defined in any one of claims 1-71, said composition comprising said at least one active agent; bringing said composition into contact with a skin of a mammal; allowing for penetration of said at least one active agent into dermis and/or epidermis; thereby obtaining said active ingredient within said dermis and/or epidermis.

83. A method for the treatment of a disease, a disorder or a condition of the dermis and/or epidermis, comprising the steps of administering to a patient in need thereof a therapeutically effective amount of a composition as defined any one of claims 1-71.