Process for producing a flat active substance administration for

Coating processes – Medical or dental purpose product; parts; subcombinations;... – Particulate or unit-dosage-article base

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Details

427 223, 424448, 424449, A01N 2500, A61J 1300

Patent

active

055694845

DESCRIPTION:

BRIEF SUMMARY
A method of high-volatile or thermolabile substances in liquid form for the production of transdermal or dermal therapeutic systems, and


BACKGROUND OF THE INVENTION

The present invention relates to a process for the production of a flat administration form having a drug portion capable of being dosed or of a flat-shaped device for the dosable release of volatile substances, such as aromatic substances, to the ambient air by using high-volatile or thermolabile dosing media in liquid or semisolid state as the ingredients of the administration form or of the device by means of printing processes, wherein a flowable preparation of the ingredients is knife-coated in a measured amount into at least one volumetrically defined sink of a flat printing block. In the production of substantially flat-shaped administration forms or devices, this process is to permit the amount of liquid active substances, liquid active substance preparations, and/or liquid active substance/adjuvant mixtures to be dosed to the other components of the administration form or device in an accurate and superficially even manner.
Such flat-shaped administration forms may, for example, be transdermal therapeutic systems, transmucosal systems, dermal, i.e., only topically effective, systems, but also those to be administered orally, such as sublingual tablets or sublingual wafers. The process is of particular value in the production of transdermal or dermal systems of the matrix type and membrane systems with a fixed reservoir.
Since the function of such transdermal or dermal therapeutic systems and the materials required for their production are well known to the skilled artisan, it is only mentioned in a few words that the active substance(s) is/are present in the usually self-adhesive systems in an at least partially dissolved form; and after application of the system on the skin they diffuse from the system into the skin, developing a local or systemic effect.
The present invention will be illustrated in the following with reference to the accompanying drawings by comparison with the state of the art.
The most simple construction is that of known, single-layer matrix systems. According to FIG. 1 they may consist of an impermeable backing layer 3, a self-adhesive matrix layer 2, and a removable protective layer 1.
The matrix layers (and the same applies to reservoir layers of the above-mentioned membrane systems) are usually manufactured in such a manner that components of the matrix and active substances, dissolved in a solvent, are coated on a suitable sheet or film (removable protective layer 1), and that the solvents are removed in a drying process. This production method may cause considerable difficulties if ingredients are required that are either incompatible with the solvents or very temperature-sensitive; or if they have an excessively high vapor pressure at the drying temperature.
Examples of thermolabile active substances include, for example, vitamin D.sub.3 -derivatives; examples of active substances having an excessive volatility include the active substances nicotine or nitroglycerin, for example. Another important group of substances used for dermal or transdermal therapeutic systems are the so-called penetration enhancers. The function of these penetration enhancers is to facilitate the passage of active substances through the skin.
Examples of high-volatile penetration enhancers include, for example, terpenes (eucalyptol, camphor, etc.); esters (ethyl acetate, ethyl propionate, etc.); alcohols (ethanol, propanol, propanediol, etc.); or ketones (methyl hexyl ketone; methyl octyl ketone, etc.).
Incompatibilities between solvents and components must be expected whenever a chemical reaction may take place between them. For instance, alcohols are used for many adhesives; these may then react with active substances which have a free carboxyl group or an ester group in the form of an esterification or transesterification.
In order to avoid these difficulties, processes have been developed wherein a liquid preparation of the p

REFERENCES:
patent: 4796381 (1989-01-01), Kauth et al.
patent: 4915950 (1990-04-01), Miranda et al.
patent: 5110599 (1992-05-01), Anhauser et al.
Korehoo KK, Patent Abstracts of Japan, vol. 016, No. 342 (C-0966) 24 Jul. 1992 JP A-04-100981, 2 Apr. 1992.

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