Transdermal therapeutic system (tts) with fentanyl as active ingredient

Abstract

The invention relates to transdermal therapeutic systems with fentanyl or an analogous fentanyl derivative as active ingredient. In order to prevent inadvertent overdosage by uncontrolled release of active ingredient as a result of damage, the active ingredient is contained in fluid-filled micro-reservoirs in the layer containing the active ingredient. The layer containing the active ingredient can optionally be provided with a membrane.

1 . A transdermal therapeutic system (TTS) containing an active substance comprising:
 a) an active substance impermeable backing layer,   b) an active substance layer,
 i.) wherein the active substance is sufentanyl, 
 ii.) where said active substance layer comprises a polymer or a polymer mixture with microreservoirs dispersed therein, 
 iii.) wherein the active substance is dissolved in the microreservoirs, and 
   c) a protective layer, which is removed before use.   
     
     
         2 . The TTS of  claim 1 , wherein the concentration of the active substance in the active substance layer is between 2 and 5% by weight. 
     
     
         3 . The TTS of  claim 1 , wherein at least 50% by weight of the active substance in the TTS is contained within said microreservoirs. 
     
     
         4 . The TTS of  claim 1 , wherein the active substance layer has a weight per unit area of between 30 and 300 g/m 2 . 
     
     
         5 . The TTS of  claim 1 , wherein the polymer is a pressure sensitive adhesive polymer. 
     
     
         6 . The TTS of  claim 1 , wherein the polymer is an amine-resistant polysiloxane. 
     
     
         7 . The TTS of  claim 1 , wherein the polymer is a polyisobutylene. 
     
     
         8 . The TTS of  claim 1 , wherein the microreservoirs have an average diameter of about 5 to 50 μm. 
     
     
         9 . The TTS of  claim 1 , wherein the fraction of the microreservoirs in the active substance layer is up to 40% by weight. 
     
     
         10 . The TTS of  claim 1 , wherein the microreservoirs further contain a liquid. 
     
     
         11 . The TTS of  claim 10 , wherein the liquid is a member selected from the group consisting of dipropylene glycol, diethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol monomethyl ether, diethylene glycol dimethyl ether, 1,3-butanediol, 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, 2-pyrrolidone or N-methylpyrrolidone or a combination thereof. 
     
     
         12 . The TTS of  claim 10 , wherein the liquid further comprises an additive which increases the viscosity. 
     
     
         13 . The TTS of  claim 10 , wherein the liquid further comprises at least one of ethylcellulose or hydroxypropylcellulose. 
     
     
         14 . The TTS of  claim 1 , wherein the active substance layer further comprises a substance which enhances the rate of permeation through human skin. 
     
     
         15 . The TTS of  claim 14 , wherein the substance which enhances the rate of permeation through human skin is selected from the group consisting of fatty acids, fatty acid esters, fatty alcohols, and glycerol esters. 
     
     
         16 . The TTS of  claim 1 , further comprising a membrane which is a distribution membrane based on an ethylene-vinyl acetate copolymer having a vinyl acetate content of between 2 and 25 wt.-% and a thickness of between 20 and 150 μm. 
     
     
         17 . The TTS of  claim 1 , further comprising a membrane which is a microporous membrane. 
     
     
         18 . The TTS of  claim 1 , further comprising a membrane and an adhesive layer which is located between said membrane and the protective layer. 
     
     
         19 . The TTS of  claim 1 , wherein the active substance is present in the form of the free base. 
     
     
         20 . The TTS of  claim 1 , wherein the active substance is present in the form of a pharmaceutically acceptable salt or as a combination of the free base with a pharmaceutically acceptable salt of said base.