Buprenorphine-wafer for drug substitution therapy

Abstract

The present invention relates to oral pharmaceutical dosage forms comprising buprenorphine with the dosage form releasing buprenorphine instantly upon oral, preferably sublingual, application of the dosage form. The present invention also relates to the use of such dosage forms for treating pain in a human or animal or for drug substitution therapy in drug-dependent human subjects.

What is claimed is: 
     
         1 . A film dosage form for trans-mucosal medication-assisted treatment for opioid addiction, the film dosage form comprising:
 a) an amount of buprenorphine, or an equivalent amount of a pharmaceutically acceptable salt thereof, sufficient to provide an average buprenorphine C max  of less than about 7 ng/ml and an average buprenorphine AUC 0-48  of less than 40 (hrs*ng)/ml;   b) naloxone or a pharmaceutically acceptable salt thereof; and   c) at least one non-gelatin polymeric film-forming material in which the buprenorphine or the equivalent amount of the pharmaceutically acceptable salt thereof and the naloxone or the pharmaceutically acceptable salt thereof, are dissolved or homogeneously dispersed;   the buprenorphine or the equivalent amount of the pharmaceutically acceptable salt thereof and the naloxone or the pharmaceutically acceptable salt thereof being present in the film dosage form in a weight ratio of from 1:1 to 10:1;   wherein, the film dosage form releases substantially all of the buprenorphine or the pharmaceutically acceptable salt thereof and approximately substantially all of the naloxone or the pharmaceutically acceptable salt thereof into contact with a mucosal surface of the oral cavity within less than 5 minutes after contacting the mucosal surface.   
     
     
         2 . The film dosage form of  claim 1 , wherein the film dosage form further comprises a pH modifier. 
     
     
         3 . The film dosage form of  claim 2 , wherein the pH modifier is selected from the group consisting of citric acid, tartaric acid, phosphoric acid, hydrochloric acid, and maleic acid. 
     
     
         4 . The film dosage form of  claim 1 , wherein the film dosage form is mucoadhesive. 
     
     
         5 . The film dosage form of  claim 1 , wherein the non-gelatin polymeric film-forming material is a modified cellulose material. 
     
     
         6 . The film dosage form of  claim 5 , wherein the modified cellulose material is a cellulose ether. 
     
     
         7 . The film dosage form of  claim 6 , wherein the cellulose ether is selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylmethylcellulose (HEMC), hydroxyethylcellulose (HEC), methylcellulose (MC), and carboxymethylcellulose (CMC). 
     
     
         8 . The film dosage form of  claim 1 , wherein the amount of buprenorphine is from 2 mg to 16 mg. 
     
     
         9 . The film dosage form of  claim 8 , wherein the amount of buprenorphine is 2 mg, 4 mg, 8 mg, or 16 mg. 
     
     
         10 . The film dosage form of  claim 1 , wherein the weight ratio is 2:1 to 8:1. 
     
     
         11 . The film dosage form of  claim 1 , wherein the film dosage form further comprises at least one of sodium dihydrogen or disodiumhydrogen phosphate, sodium tartrate, sodium ascorbate, citric acid, tartartic acid, adipinic acid, ascorbic acid, acetic acid, or lactic acid. 
     
     
         12 . The film dosage form of  claim 1 , wherein the film dosage form exhibits a t max  from approximately 45 to approximately 90 minutes. 
     
     
         13 . The film dosage form of  claim 1 , further comprising a flavoring agent. 
     
     
         14 . The film dosage form of  claim 13 , wherein the flavoring agent is selected from the group consisting of mint, raspberry, licorice, orange, lemon, grapefruit, caramel, vanilla, cherry, grape, and combinations thereof.