HK1026356B - Method for producing transdermal patches (tts) - Google Patents

Description

The invention relates to a process for the manufacture of transdermal therapeutic patches (TTS) as defined in claim 1.

DE-PS 32 04 582 provides a method for continuous preparation and filling of patch packs with an active substance for transdermal administration, whereby the active substance is applied in portions at intervals to a carrier film, covered with metallic cover film sections and then covered with an intermediate film using an elastic adhesive film directed towards this adhesive film on one side, and then the active substance portions with the surrounding film layers are removed to the desired size.

A process for continuous production of transdermal therapeutic patches is also known, whereby a laminate is first produced by coating an intermediate film with a fluid active substance preparation, and then cut into strips of a specified width and, in further steps, into active substance sections of a specified length, which are applied at specified intervals to a protective film covering all the sides and finally cut through the protective film to the band passage between the active substances sections in a single layer.

Another process is described in DE-OS 41 10 027, which describes a process for continuous production of transdermal therapeutic patches which have a back layer, an adhesive active substance reservoir layer and a removable protective layer, minimising the loss of active substance during packaging. In this process, the adhesive active substance reservoir in the form of a laminate consisting of an active substance adhesive layer and a polymer film is transferred to the later protective layer by means of a donor edge. However, the disadvantage of this method is that the final product always has two polymer carrier layers after removal of the protective layer, which gives a total stiffness so high that a satisfactory TTS is not given in every case.

The purpose of the present invention is therefore to transfer isolated active substance-containing sections with high speed, high precision and without loss of active substance from a first track at predetermined intervals in succession to a second track preferably transversing the sections in a technically simple and reliable manner, while avoiding that the carrying comfort of the final product is impaired by a polymer film within the TTS.

This problem is solved according to the invention by a method according to claim 1, which is all the more remarkable since it was previously considered by experts to be a fixed rule of technical conduct that adhesive films can only be transferred in the form of laminates with rigid surface shapes.

Although transfer methods are described in DE-OS 41 10 027, DE-OS 15 11 873, DE-PS 25 55 910, DE-OS 32 33 546, DE-PS 36 18 542 and DE 42 32 279, they never indicate the possibility of removing the process film when the self-adhesive laminate is transferred.

The manufacture of the patch according to the invention may be carried out in a number of different layers, depending on the need, i.e. the purpose for which the patch is to be used, each layer being made of suitable materials such as metals, preferably aluminium, polymers or textile surfaces. The individual layers may be self-adhesive or adhesive-repellent, permeable or impermeable to the active substance, flexible or inflexible according to their respective purpose.

The active substance sections may be of different shapes, such as rectangular, square, oval or circular, but a rectangular or square shape is preferred to avoid loss of active substance.

The polymers used to produce the active substance and the possible additives dependent on the active substance are, for example, plasticizers, adhesives, stabilizers, carriers, additives regulating diffusion and penetration or fillers. The physiologically safe substances in question are known to the professional. The self-adhesive properties of the active substance are intended to ensure permanent contact with the skin.

For example, a protective layer of the active substance before application may be made of the same materials as the back coat, but these must be made removable, for example by silicone treatment.

The process and auxiliary layers may be made of the same materials. The adhesive layers may be made from a polymer matrix with a base polymer and, where appropriate, common additives. Suitable materials are, for example, silicone, rubber, synthetic homo-, co-, or block polymers similar to rubber, polyacrylates and their copolymers and also esters of hydrated colophonium. In principle, all polymers used in the manufacture of adhesives are suitable and physiologically safe. In particular, those that are preferably block polymers based on styrene and 1,3-diene, polyisobutylene or polymers and copolymers of acrylate and/or m-crylate.

The active substances are those applied to the skin without or with absorption agents and which produce a local or systemic effect.

Substances with local action are e.g. antiperspirants, fungicides, bactericides and bacteriostatics.

Substances with systemic effects are, for example, antibiotics, hormones, antipyretic drugs, antidiabetic drugs, coronary heart disruptors, cardiac glycosides, spasmolytics, antihypertensive drugs, psychotropic drugs, migraine medicines, corticosteroids, analgesics, contraceptives, anti-rheumatic drugs, cholinergics or anticholinergics, sympathomimetics or sympatholytics, vasodilators, anticoagulants or antiarrhythmics.

The invention is shown in the figure in examples of execution and is illustrated by these below.

In Figure 1, (1) means the first rail laminate or rail, consisting from top to bottom of a siliconised at least one-sided foil (3) support layer, an adhesive layer (4) containing the active substance and a support layer (9) (at least one-sided siliconised).

In the first movement, the film (3) and the active layer (4) are cut perpendicular to the direction of the rail with a straight cut, so that, for example, square sections (3',4') are formed. The siliconised support layer (9) is not cut. The rail (1) is transported from right to left by means of a pinch guard, which may be replaced by a roller guard or similar, and then held by a support. Immediately after the layers (3) and (4) are cut, the laminate (5), consisting of an adhesive-reinforced profile, is glued to the adhesive-shaped laminate (1) on the side of the first layer (3). (11) The adhesive guard is glued to the adhesive-shaped laminate (1) on the side of the first layer. (4) The first layer of the transfer is glued to the adhesive-shaped laminate (1) by means of a gluing device.

The sections (3') of the layer (3) are then removed from the active substance-containing adhesive sections (4') via a second donor edge (12) and the sections (4') are then glued to the second layer (2). The directions of all tracks are indicated by arrows. The entire surface of the second track (2) is covered by a laminate consisting of a non-active adhesive layer (13) and an active opaque film (14) (back layer) (Fig. 2). The grid-like intersection of layers 13 and 14 between the sections (4') is removed and (2) is cut to obtain the individual paving (Fig. 2).

The active adhesive layer (4) may, for example, contain 57% solution polyacrylate, 25% plasticizer, 10% polymethacrylate and 8% physostigmine at a thickness of 100 g/m2. At a width of 35 mm, it is possible to obtain square paving formats (4') of 35 x 35 mm. The second layer (2) is approximately 55 mm wide and may be made of double siliconized polyester film (PET).

Claims (3)

1. A process for the continuous production of transdermal therapeutic patches, wherein a laminate of an auxiliary layer (3) siliconized at least on one side, an active substance-containing, pressure-sensitive adhesive layer (4), and a supporting layer (9) is prepared as a strip-shaped web (1) first, and the active substance-containing sections (4') obtained by punching said layers (3) and (4) across the web direction are intermittently transferred on a second web (2), the punching procedure taking place in the rest phase between the cycles and the transfer procedure onto the second web (2) being carried out preferably at equal distances by means of a transfer device (11, 12), characterized in that the supporting layer (9) is stripped from the active substance-containing sections (4') during the transfer first, and that then the sections (3') of the auxiliary layer are removed with the aid of a process layer (5) which has been rendered pressure-sensitive adhesive.
2. The process according to claim 1 characterized in that the strip-shaped web (1) and the second web (2) are intermittently forwarded at differing movement and rest phases, and/or differing step lengths, and/or differing rates.
3. The process according to claim 1 characterized in that the transfer devices are moved to-and-fro in web direction during the transfer of the active substance-containing sections (4').