Transdermal therapeutic system for the administration of physost

Details Transdermal therapeutic system for the administration of physost Transdermal therapeutic system for the administration of physost

1995-07-12

1997-12-16

Phelan, D. Gabrielle

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Web, sheet or filament bases; compositions of bandages; or...

424447, 424449, A61F 1302

Patent

active

056982160

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/EP93/02970, filed Oct. 27, 1993.
The invention relates to a transdermal therapeutic system containing physostigmine as active component, and to a process for the production thereof.
The application of physostigmine, for example for the treatment of Alzheimer's disease has been described in the literature several times, whereby the efficacy of the substance was judged differently. Since the alkaloid exhibits a high first pass effect--the bioavailability of physostigmine after oral administration is in the range of 5%--the differing results must be attributed to different forms of application.
DE-OS 35 28 979 describes a composition which in addition to physostigmine contains a medium-chain carboxylic acid; this composition can be applied on a bandage, an insert or a compress, which are applied by means of a dressing. With this kind of application, which is not a TTS per se, it is intended to provide the bandage, compress or insert with an inner reservoir layer, an impermeable protective barrier foil or an impermeable protective film and to apply a diffusion controlling membrane between the reservoir and the skin. Neither the diffusion controlling membrane nor the protective foils are described in detail. The carboxylic acids are explicitly mentioned to be effective carriers for the administration of the pharmaceutic through the skin which otherwise would not be able to penetrate through the skin barrier. However, this statement is not tenable from the scientific point of view. DE-PS 36 06 892 describes a retarded application of physostigmine and other active substances, which application may be carried out transdermally. A special formulation is not disclosed. What is more, reference is made to a pre-described formulation (U.S. Pat. No. 3,921,363).
A further publication describing the application of physostigmine is WO 91/15176. This publication does not go beyond the teaching of the German Patent DE 38 43 239 discussed hereinbelow. Apart from the only vague statements concerning the transdermal therapeutical systems, neither of the two publications mentioned hereinabove deal with the instability of physostigmine, which instability was realized very early. In this respect, however, reference may be made, for example, to the following literature dealing with the instability of physostigmine: (Eber, W., Pharmaz. Ztg. 37, 483 (1888), Herzig, J., Mayer, H., Mh. Chem. 18, 379 (1897); Herzig, J., Lieb, H., ibidem 39, 285 (1918); Salway, A. A., J. Chem. Soc. (London) 101, 978 (1912)).
Owing to a rapid decomposition of the active substance, this instability severely limits the use of physostigmine in pharmaceutics.
The problem of the rapid decompostion of physostigmine in a TTS is also dealt with in DE 38 43 238 and DE 38 43 239. The TTS described in DE 38 43 239 exclusively contains lipophilic softeners, whereas the system described in DE 38 43 238, apart from lipophilic softeners, contains carboxylic acids with rather long chains, viz oleic acid or undecene acid, as solvents for physostigmine. These fatty acids, as well, are lipophilic substances. Thus, the two systems have in common that physostigmine is released to the skin from a lipophilic matrix securing the stability of the active substance.
Surprisingly, it was found by way of controls that TTS prepared according to the teachings of the patent specifications DE 38 43 238 and DE 38 43 239 do not satisfactorily meet the strict requirements which must be applied to the self-adhesiveness of a TTS. Tests in which the TTS were worn brought the result that in the case of some of the test persons the TTS, after having been worn for only 8 hours, did no longer adhere with their entire surface. After 24 hours, 10% of the test persons had lost the TTS, and in the case of 15% of the test persons there was no longer an all-over skin contact. Only in the case of 75% of the test persons was the adhesive behaviour of the TTS satisfactory. However, TTS which adhere only with 75% of the test persons or patients without giving cause for compl

REFERENCES:
patent: 5370924 (1994-12-01), Kochinke
patent: 5391375 (1995-02-01), Hille
Salway, J. Chem. Soc. (London) 101, pp. 978-989 (1912).

Affiliated with

Also associated with

Rating

Transdermal therapeutic system for the administration of physost does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Transdermal therapeutic system for the administration of physost, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transdermal therapeutic system for the administration of physost will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-203109