HK1177698A - Low toxicity topical active agent delivery system - Google Patents

Description

Low toxicity topical active agent delivery system

Cross Reference to Related Applications

This application claims priority from U.S. provisional application No. 61/286,668 filed on 12/15/2009 and U.S. patent application serial No. 12/711,381 filed on 24/2/2010, both of which are incorporated herein by reference in their entirety.

Technical Field

The present invention relates to compositions for the topical delivery of active agents. The compositions relate to the delivery of active agents to the skin with reduced toxicity, such as dryness, irritation, or inflammation. The compositions of the present invention are directed to the delivery of topical agents such as retinoids to the skin.

Background

Lipophilic skin care actives such as retinoids are often applied topically to reduce the appearance of aging for other cosmetic purposes, or to treat skin conditions such as acne.

The comfort associated with the application of topical agents is related in part to the evaporation rate of the applied composition on the skin. Products with a slow evaporation rate may feel greasy on the skin, while products with an excessively fast evaporation rate feel as if they were not applied to the skin at all or leave the user with the impression of insufficient application, which may lead to overuse. Combining the topical agent with a volatile silicone allows for a suitable evaporation rate to provide satisfactory application. However, silicones by themselves are poor solvents for hydrophobic active agents.

To address poor solubility in silicones, delivery systems for these agents typically require 35% or more organic solvent as a carrier to solubilize the active agent and to provide suitability for combination with volatile compounds that provide satisfactory application by the user. Alcohols such as ethanol are preferred in the prior art as organic solvents.

Many active agents promote thinning or drying of the skin. The problem is exacerbated by the inclusion of significant levels of organic solvents that themselves can alter epidermal barrier lipids and contribute to skin irritation. Ethanol, as used in the retinoid compositions of U.S. Pat. No. 4,826,828, incorporated herein by reference, is considered a solution for topical delivery of hydrophobic agents. In contrast, ethanol promotes skin irritation and dryness. Thus, combining ethanol with a irritating active agent increases skin dryness, which leads to non-optimal use.

Thus, there is a need for hydrophobic active agent delivery systems that provide satisfactory applications and do not contribute to toxicity.

Disclosure of Invention

The following summary is provided to facilitate an understanding of some of the innovative features unique to the present invention and is not intended to be a full description. A full appreciation of the various aspects of the invention can be gained by taking the entire specification, claims, drawings, and abstract as a whole.

Active agent delivery compositions are provided that result in satisfactory application of the active agent to the skin of a subject without leaving a greasy feeling residue. The inventive compositions include active agents, illustratively: vitamin a or a derivative thereof; a hydroxy acid; benzoyl peroxide; resorcinol; an antibacterial agent; an anti-neoplastic agent; an antiviral agent; non-steroidal anti-inflammatory drugs; UV filters (UV filters); a lipid; and an immunomodulator. The active agent is optionally vitamin a or a derivative thereof present between 0.001 to 2 weight percent. Optionally, the vitamin a derivative is retinal, retinoic acid, retinyl ester, retinol, tretinoin, isotretinoin, adapalene (adapalene), tazarotene (tazarotene), or a combination thereof. The active agent is optionally salicylic acid, acetylsalicylic acid, or a combination thereof.

The compositions of the present invention provide satisfactory dermal application by the use of a silicone carrier, optionally a linear aliphatic polyorganosiloxane, optionally ethyltrisiloxane.

Polyhalogen carriers (vehicles) are present in the compositions of the present invention to solubilize the active agent with the carrier while reducing or eliminating the need for organic solvents such as ethanol. The carrier is optionally a perfluoroether (perfluor ether), optionally methoxynonafluorobutane (methoxynonafluorobutane) or ethoxynonafluorobutane (ethoxynonafluorobutane). The carrier is optionally present at about 15 to 25% by weight.

Including an optional organic solvent. Optionally, the organic solvent is present at less than 25% by weight. Optionally, the organic solvent is present at less than 5% by weight.

Methods of treating a skin disorder in a subject are also provided. The skin disorder may be, for example, acne, wrinkles, dryness, cancer or perspiration. The inventive method comprises applying the inventive composition to the skin of a subject.

Detailed Description

It is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

The present invention has utility as a topical delivery system for active agents. The present invention has more specific utility for delivering hydrophobic active agents to the skin with reduced medicament or solvent related side effects and improved comfort and user compliance.

The compositions of the present invention comprise an active agent in combination with a carrier and a compatible carrier.

As used herein, the term "active agent" refers to a molecule suitable for delivery to the skin of a subject. Preferably, the active agent has pharmaceutical activity and is present for the treatment or prevention of a skin disorder. Optionally, the active agent is a low polarity molecule, such as those having a hydrocarbon chain of three or more carbons, but may also include higher polarity materials. Examples of active agents illustratively include: vitamin a or a derivative thereof; a hydroxy acid; aromatic molecules such as benzoyl peroxide and resorcinol; antibacterial agents such as azelaic acid, erythromycin, sodium sulfacetamide, tetracycline and derivatives, and clindamycin; antineoplastic agents and/or ophthalmic agents illustratively including 5-fluorouracil, doxorubicin, imiquimod and sodium [ o- (2, 6-dichloroanilino) phenyl ] acetate; antiviral agents, illustratively ganciclovir (ganciclovir), trifluorothymidine and related compounds; nonsteroidal anti-inflammatory drugs, illustratively flurbiprofen, ibuprofen, naproxen, indomethacin, and related compounds; antimitotic drugs, illustratively colchicine taxol and related compounds; drugs that act on actin polymerization, illustratively antimuscarinic cyclopeptides, cytochalasin B and related compounds; inhibitors of dihydropyrimidine dehydrogenase (DPD), Thymidine Phosphorylase (TP) and/or Uridine Phosphorylase (UP); ultraviolet (UV) filters, illustratively benzophenone derivatives such as oxybenzone, octocrylene, octyl methoxycinnamate and avobenzone; a radioactive agent, illustratively a fluorouracil such as 6-and 4-fluorouracil; and immunomodulatory molecules such as tacrolimus and pimecrolimus. The active agent need not have pharmaceutical activity. Other active agents are illustratively cosmetic agents, such as pigments, dyes, and fillers. It is understood that the inventive compositions optionally include more than one active agent. Optionally, 2, 3, 4, 5, 6 or more active agents are present in the inventive compositions. Optionally, the active agent is a prodrug that is converted to the desired active species, optionally in the skin or layers thereof.

Optionally, the active agent is a lipid, such as those suitable for controlling perspiration. Optionally, the lipid has an HLB of less than about 12, less than about 8, or optionally less than about 6. Illustrative examples of lipids include glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, sorbitan monoisostearate, sorbitan monocaprylate, sorbitan monoisooleate, glyceryl monolaurate, glyceryl monocaprylate, glyceryl monocaprate, mixtures thereof, and the like. Optionally, the lipid is glycerol monolaurate, available from suppliers such as Fitz Chem Corporation under the name MONOMULS 90-L12.

Generally, lipids comprise from about 4 to about 35%, and optionally from about 5 to about 20%, and optionally from about 10 to about 15%, by weight of the composition, based on the total weight of the composition, and including all ranges subsumed therein.

Examples of pigments illustratively include inorganic or organic molecules, such as molecules in the form of metal lakes. The pigment is illustratively made from: titanium dioxide; zinc oxide; d & C red No. 36 and D & C orange No. 17; calcium lakes of D & C red nos. 7, 11, 31 and 34; barium lake of D & C red No. 12; d & C Red No. 13 strontium lake; aluminum lakes of FD & C yellow No. 5, FD & C yellow No. 6, D & C red No. 27, D & C red No. 21, and FD & C blue No. 1; iron oxide; manganese violet; chromium oxide and ultramarine blue.

Examples of vitamin a or its derivatives illustratively include retinoids such as retinal, retinoic acid, retinyl esters, retinol, tretinoin, isotretinoin, adapalene, tazarotene and the like.

Examples of hydroxy acids illustratively include beta hydroxy acids such as salicylic acid, acetylsalicylic acid, and the like.

Although illustrative examples using retinol as the active agent are described, the specification is not limited thereto. Other active agents may function similarly herein.

A wide variety of skin or systemic diseases are treatable with the compositions of the present invention, illustratively including acne, wrinkles, dryness, eczema, psoriasis, actinic and non-actinic keratosis, rosacea (rosaceuos), and the like. U.S. patent No. 3,932,665 describes retinal as a therapeutic agent by topical application in a method for treating acne. The disclosure of U.S. patent No. 3,932,665 is hereby incorporated by reference herein. Topical application of 5-fluorouracil for the treatment of keratosis is described in U.S. patent No. 4,034,114, the contents of which are incorporated herein by reference. The compositions of the present invention reduce the side effects typically associated with topical or ocular administration of active agents.

The compositions of the present invention are suitable for topical delivery of active agents. The compositions of the present invention illustratively comprise retinol formulated in a carrier comprising a volatile silicone. With such a carrier, the level of retinol required to achieve a beneficial effect is minimized and the potential for skin irritation by retinol is greatly reduced. Furthermore, retinol is stable when formulated in silicones comprising the compositions of the present invention, as compared to other conventional carriers.

The compositions of the present invention may comprise from 0.005 to 1.0 weight percent retinol, in which case they are optionally applied directly to the skin, or supplied as a more concentrated solution containing higher levels of active agent, in which case they are optionally diluted to the desired level with a cosmetically acceptable carrier, for example from 0.005 to 1.0 weight percent for retinol, prior to application. In the formulations of the present invention, water is optionally minimized or eliminated to improve the stability of retinol and minimize the possibility of oil and water separation. Optionally, water is present at less than 2%. One skilled in the art will recognize that different levels of active agent will be feasible herein depending on the final amount of active agent desired.

Optionally, the active agent is present in an amount less than 30% w/w. Optionally, the active agent is present at a weight percentage of 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.01, 0.001, 0.0001, at any level therebetween or any range therein. Optionally, the active agent is present at 20% w/w. Illustratively, when azelaic acid is the active agent, it is present at 15 to 25% w/w. The vitamin a derivative is optionally present at 0.001 to 2% by weight. Imiquimod is optionally present at 3 to 8% by weight. It is within the skill of the art to determine the optimal level of active agent in a concentrated solution or final solution of an application.

The active agent is preferably provided in a carrier. The carrier is optionally present at 10 to 75% w/v. Optionally, the carrier is a volatile compound, such as a volatile siloxane. The siloxane is illustratively a cyclic siloxane or an acyclic siloxane. Examples of cyclic siloxanes illustratively include cyclic polydiorganosiloxanes, cyclotetradimethicones and cyclopentadidimethicones. Linear organopolysiloxanes are illustratively alkyl-, alkoxy-or phenyl polydimethylsiloxanes, and alkyl-, alkoxy-or phenyl polytrimethylsiloxanes. Optionally, the carrier is an aliphatic volatile siloxane. The aliphatic volatile siloxane optionally has two to six silicon atoms. Optionally, the aliphatic volatile siloxane is a linear polyorganosiloxane, for example a polyorganosiloxane having 2 to 6 silicon atoms, optionally a trisiloxane. Optionally, the carrier is ethyl trisiloxane. It is to be understood that the inventive compositions optionally include more than one carrier.

Optionally, the volatile silicone is a lightweight carrier that evaporates after application and thus has an excellent lightweight "feel" on the skin. Volatile silicones are generally limited in their ability to dissolve low polarity (i.e., generally greater than C7-C8)) organic compounds such as retinoids. For example, when relatively low therapeutic levels of retinol (0.1-0.2% w/v) are dissolved in cyclomethicone alone, a cloudy solution results due to incomplete solubilization of the silicone fluid.

Among the nearly limitless possibilities of vehicles that can function with both active agents and volatile silicones, it has been unexpectedly discovered that organic polyhalogen vehicles can incorporate appropriate therapeutic levels of retinoids and reduce hydrocarbon solvents to levels of less than 5% compared to U.S. Pat. No. 4,826,828, which requires 35-60% w/w hydrocarbon solvent. The organopolyhalogen solvent is optionally described in U.S. patent nos.: 6,251,375, the contents of which are incorporated herein by reference. In particular examples, the carrier incorporates a halogen such as one or more fluorine atoms. In some specific examples, the carrier is a perfluoroether. In some specific examples, the carrier is methoxynonafluorobutane or ethoxynonafluorobutane, available from 3M Specialty Materials, st. The carrier optionally has a boiling point of less than 78 ℃. Optionally, the carrier has a boiling point of less than 65 ℃. The carrier is optionally present at a final concentration of about 5% to 40% w/w. Optionally, the carrier is present at 15% to 25% w/w. Optionally, the carrier is present at 20% w/w. It is understood that optionally, more than one carrier is present in the inventive composition. Optionally, 2, 3, 4, 5, 6 or more carriers are present in the inventive composition.

Optionally, the compositions of the present invention are formulated with a level of organic solvent. Optionally, the organic solvent is volatile at ambient temperature and pressure. Optionally, less than 35% organic solvent is included. Optionally, less than 30% organic solvent is included. Optionally, the level of volatile organic solvent is less than 15% w/w. Optionally, the organic solvent is present at 5% or less w/w. Optionally, no organic solvent is present. Optionally, the organic solvent is an alcohol, illustratively ethanol. Optionally, the alcohol is ethoxydiglycol, ethanol or isopropanol. Optionally, the organic solvent is ethoxydiglycol present at 10% w/w or less. Optionally, ethoxydiglycol is present at 3% w/w. In contrast to the prior art, which requires much higher concentrations of volatile organic solvents such as ethanol, the levels of organic solvents optionally do not cause significant drying or other toxic effects on the skin. It is to be understood that more than one organic solvent is optionally present in the inventive composition. It is further understood that the compositions of the present invention are completely free of ethanol.

A particularly unexpected and surprising discovery of the subject invention is that stable solutions of the active compound in a carrier, when combined with 5% to 40% w/w of the carrier, can be prepared with less than 15% w/w of an organic solvent. It is particularly surprising that 5% to 40% w/w of the carrier can facilitate the production of stable soluble solutions with less than 5% organic solvent.

Optionally, the compositions of the present invention include other additives or pharmaceutical carriers, illustratively including: stabilizers such as antioxidant BHT; a surfactant, illustratively Laureth-4; antioxidants, illustratively vitamins C and E, and green tea extract (i.e., tea tree (camellia sinensis)) or SILOX GT from colorative Labs, Stony Brook, NY; and a lubricant, illustratively a mixture or single component of lubricants available from Symrise, Teterboro, NJ under the trade name SYMREPAIR. One skilled in the art will readily appreciate that additives are suitable for use with the present invention, for example, to provide desired flow characteristics, absorption, evaporation, delivery of the active agent, conversion of the prodrug, or other desired characteristics.

The compositions of the present invention are also optionally diluted to the appropriate active level for use by use of other topically acceptable compounds or carriers that are optionally miscible with retinol or other active agents of the present invention. Other cosmetic additives are optionally used in the compositions of the present invention when those compositions are used or diluted with a suitable carrier.

The formulated compositions described herein are optionally topically applied to the skin after concentration, which results in the application of 0.005 to 1.0 weight percent, optionally 0.01 to 0.50 weight percent, of retinol. The active agent is optionally applied to areas where fine lines, wrinkles, dry or inelastic skin or large hair holes are observed. Optionally, a moisturizing agent is applied with or after application of the present composition to enhance the tactile comfort associated with application of the composition and to enhance wrinkle lifting and other benefits achieved by the composition. The improved properties of the compositions of the present invention are that no additional moisturizers need to be used.

Optionally, the wetting efficacy is achieved in the present composition comprising retinol, thereby obviating the need for a separate moisturizing agent. Thus, optional compositions of the present invention are formulated to include a wetting component compatible with the silicone carrier at a level of up to 35% by weight of the final formulation. Preferred moisturizing ingredients suitable for use in preferred compositions of the invention are illustratively petrolatum, ethylhexyl palmitate, cholesterol fatty acid ceramide, and squalene. The addition of one or more moisturizing components is beneficial when the compositions of the present invention are applied to previously dry skin or are under conditions where drying typically occurs, for example, in cold climates or during the winter months. Optionally, the moisturizing component is applied when the active agent itself has a drying effect, for example when retinol or 5-fluorouracil is applied.

By daily application of a composition comprising retinol, the skin texture, color and tone will be improved. Wrinkles and fine lines are reduced with minimal irritation.

The inventive compositions are optionally applied to the skin of a subject. The subject is optionally a patient. The subject is optionally a mammal such as a human, non-human primate, horse, goat, cow, sheep, pig, dog, cat, and rodent.

The inventive composition is optionally provided as a lotion, cream, gel, strip (bar), ointment, or in the form of a pad (pad). Optionally, the composition is provided in a single use container, the contents of which are applied directly to the stratum corneum of the subject or to an applicator pad for subsequent delivery to the subject.

After application of the composition according to the invention, the cooling effect is optionally observed. Cooling as used herein means reducing the skin temperature after application, optionally from about 1 to about 2 ℃. The cooling effect includes the effect from evaporation of the carrier or vehicle.

The compositions of the present invention are optionally administered one to three times per day. Optionally, the compositions of the present invention are delivered once daily. Optionally, the compositions of the present invention are administered once a week, once two weeks, once a month, or any subdivision thereof. It is understood that the compositions of the present invention are administered for an amount of time appropriate to the efficacy of the active agent. Optionally, the composition of the invention is administered for one to six weeks. Optionally, the compositions of the present invention are administered indefinitely.

Methods of formulating the inventive compositions for optionally satisfactory application to the skin of a subject are also provided. The inventive process illustratively comprises preparing a first solution by solubilizing one or more active agents, optionally in an organic solvent, preferably with gentle mixing under low to no light conditions.

The second solution is prepared by mixing additives such as emollients and vitamins. The second solution is added to and mixed with the first solution. The mixing is preferably carried out in the dark under mild mixing conditions.

A third solution of the carrier and vehicle is prepared and added to the mixed first and second solutions to form the composition. Mixing is optionally gentle mixing without vortexing in low light or dark. Mixing preferably lasts 120 minutes. The composition is preferably stored under an inert gas such as nitrogen.

It should be understood that low to no light conditions are important if a photoactive component is present in the subject invention. The process of the present invention is optionally carried out under ambient or other lighting conditions in the absence of a photoactive component.

The process of the invention is optionally carried out under ambient temperature and pressure conditions. Optionally, the process of the invention is carried out by heating one or more components or solutions.

Various aspects of the invention are illustrated by the following non-limiting examples. This example is for illustrative purposes and is not intended to limit any practice of the invention. It is to be understood that variations and modifications may be made without departing from the spirit and scope of the invention. Those skilled in the art will readily understand how to synthesize or commercially obtain the reagents and components described herein.

Example 1:

blend formula a compositions comprising 3.0% ethoxydiglycol, 0.5% Laureth-4, 0.10% hydroxypinolone retinoic acid ester (hydroxypinocolone retinoate), 0.05% BHT, 2.0% SYMREPAIR, 2.0% tetrahexyldecyl ascorbate (Tetrahexyldecylascorbate), 0.50% tocopherol, 20% methoxynonafluorobutane, 1.0% SILOX GT, and the balance ethyltrisiloxane.

Formulation A was prepared using low light conditions by mild mixing in a paddle mixer to produce solution 1, which solution 1 contained ethoxydiglycol (Transcutol CG, available from Gattefose, Toronto, ON, Canada), Laureth-4(Croda, Edison, NJ), hydroxy pinacolone retinoic acid ester (MDI-101, Concert LLC), and BHT. Solution 2 was prepared separately. Solution 2 included SYMREPAIR (Symrise, inc., terboro, NJ), SYMREPAIR included hexyldecanol, bisabolol, cetyl hydroxyproline palmitate, stearic acid, and Brassica campestris (Brassica campestris) sterols. SYMREPAIR was mixed with tetrahexyldecyl ascorbate (BV-OSC, Barnet, Englewood Cliffs, NJ) and tocopherol USP in a paddle mixer until a clear solution formed. Solution 1 was mixed with solution 2 using continuous, non-vortex paddle mixing, with slow addition, protecting the solution from light. Solution 3 was prepared by gentle paddle mixing at ambient temperature. Solution 3 included ethyltrisiloxane (Silsoft ETS, Monentiv, Albany, NY), CF-61(3M Specialty Materials), and SILOX GT (a combination of cyclopentasiloxane and tea tree leaf extract from BASF Beauty Care). The combined solutions 1 and 2 were slowly added to solution 3, with continuous, non-vortex paddle mixing, protecting it from light. Mixing continued for 120 minutes.

Formulation a was transferred to an opaque holding container with nitrogen headspace for storage. 60mL of formulation A was then transferred to a 2oz. amber glass bottle with purified nitrogen headspace and stored, protected from light until use.

Preparing a comparator solution comprising 46.3% cyclomethicone-tetramer; 35% dry alcohol SD 40B; 5% ethylhexyl palmitate; 5% octyl dimethyl PABA; 2% benzophenone-3; 2% deionized water; 2% neopentyl glycol dicaprate; 1.5% ethylcellulose K5000; 0.22% butylhydroxytoluene; and 1% retinoid mixture. Formulation B was prepared substantially as described in U.S. patent No. 4,826,828, the contents of which are incorporated herein by reference.

Example 2:

half-face test (split face test) was performed by using formulation a or the comparative as follows. Twelve women aged 20 to 59 years applied formula a to one side of their face and the comparator to the other side once a day for eight weeks. Thin slices of skin on each side of the face were removed before the start of the test and after the eight-cycle test period. All twelve women in the formula a group and nine out of the twelve women in the comparative group were in better condition for the skin shavings after the test as compared to the skin shavings before the test. All women had thicker and more ordered skin after the test than before the test. All women in formula a group reported increased moisture in the test skin, while the comparative group produced symptoms of dryness and cracking in the tested skin area.

Example 3:

the ability of an electrical current to flow through the stratum corneum provides an indirect measure of the water content of the stratum corneum. The moisture retention (momturization) of the participants participating in the study in example 2 was evaluated using an IBS impedance/conductivity meter. At least twelve hours elapsed between the final product application and the skin conductance measurement. The data show that the formula a treated side was more moist (higher conductance readings at all measurement time points) than the comparative side. The comparative side of the face did not show similar levels of relative moisture content. Thus, targeted measurements and demonstrations of stratum corneum conductivity showed a significant increase in facial skin moisture content.

Example 4:

the example 1 formulation a composition was tested for its ability to reduce skin dryness relative to the comparative, with or without supplemental moisturizing agents. Twelve participants who showed dry skin after repeated soap washing were selected for participation in the study. Initially, participants washed their hands with a bar soap to bring about a dry state. The test formulation was applied daily to one hand while the other hand was left untreated to serve as the control side. Each hand was randomly evaluated by two trained evaluators who did not know which hand was being treated. Evaluators use stereomicroscopes to help them perform their evaluations. The results of this study demonstrate that the unwetted comparative side showed additional dryness compared to the control hand. The dryness level was improved by applying a moisturizer after each comparative application. In comparison, formula a treated hands showed a significant increase in moisture content. The addition of moisturizers after each application of formula a did not significantly increase the moisture content of the treated skin. The benefits of formula a lasted twenty-four hours after final treatment, indicating that the formula a composition provided effective long-term moisturization.

Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

Patents and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These patents and publications are herein incorporated by reference to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

The above description is illustrative of particular embodiments of the invention and is not meant to be limiting upon the practice thereof. The following claims, including all equivalents thereof, are intended to define the scope of the invention.

Claims (19)

1. A topical active agent delivery composition comprising:

an active agent;

a silicone carrier; and

an organic polyhalogen carrier.

2. The composition of claim 1, wherein the agent comprises one or more members selected from the group consisting of: vitamin a or a derivative thereof; a hydroxy acid; benzoyl peroxide; resorcinol; an antibacterial agent; an anti-neoplastic agent; an antiviral agent; non-steroidal anti-inflammatory drugs; a UV filter; a lipid; or an immunomodulator.

3. The composition of claim 2, wherein the agent is vitamin a or a derivative thereof and is present between 0.001 to 2 weight percent.

4. The composition of claim 3, wherein the vitamin A derivative is selected from the group consisting of: retinal, retinoic acid, retinyl ester, retinol, tretinoin, isotretinoin, adapalene, tazarotene, or combinations thereof.

5. The composition of claim 2, wherein the hydroxy acid is salicylic acid, acetylsalicylic acid, or a combination thereof.

6. The composition of claim 1, wherein the silicone carrier is a linear aliphatic polyorganosiloxane.

7. The composition of claim 6, wherein the silicone carrier is ethyl trisiloxane.

8. The composition of claim 1, wherein the carrier is a perfluoroether.

9. The composition of claim 1 or 8, wherein the carrier is methoxynonafluorobutane or ethoxynonafluorobutane.

10. The composition of claim 1, wherein the carrier is present at about 5% to 40% by weight.

11. The composition of claim 1, wherein the carrier is present at about 15% to 25% by weight.

12. A topical active agent delivery composition comprising:

retinol, said retinol being present between 0.005% and 1% by weight;

a volatile silicone carrier; and

a methoxynonafluorobutane carrier, said carrier present at about 5% to 40% by weight.

13. The composition of claim 12, wherein the volatile silicone carrier is a linear aliphatic polyorganosiloxane.

14. The composition of claim 13, wherein the volatile silicone carrier is ethyl trisiloxane.

15. A method of treating a skin disorder in a subject, comprising:

applying to the skin of a subject the composition of claim 1, 2 or 12.

16. The method of claim 15, wherein the subject is not a human.

17. A topical active agent delivery composition comprising:

an active agent;

a linear organopolysiloxane carrier;

a methoxynonafluorobutane carrier present at about 5% to 40% by weight; and

less than 25% by weight of an organic solvent.

18. The composition of claim 17, wherein the organic solvent is ethoxydiglycol.

19. The composition of claim 17, wherein the organic solvent is present at less than 5% by weight.