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 sublingual dosage form comprising:
 a. a non-gelatin polymeric film-forming material;   b. an amount of buprenorphine or a pharmaceutically acceptable salt thereof; and   c. an amount of naloxone or a pharmaceutically acceptable salt thereof;   wherein
 the buprenorphine or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in the sublingual dosage form in a weight ratio of from 1:1 to 10:1; 
 the sublingual dosage form releases substantially all of the buprenorphine or pharmaceutically acceptable salt thereof in less than 5 minutes upon sublingual administration; 
 the amount of buprenorphine or pharmaceutically acceptable salt thereof delivered by the sublingual dosage form results in a buprenorphine C max  of less than about 7 ng/ml and an AUC 0-48  of less than 40 (hrs*ng)/ml; and 
 the sublingual dosage form is a film. 
   
     
     
         2 . The dosage form of  claim 1 , wherein the non-gelatin polymeric film-forming material is a modified cellulose material. 
     
     
         3 . The dosage form of  claim 2 , wherein the modified cellulose material is a cellulose ether. 
     
     
         4 . The dosage form of  claim 3 , wherein the cellulose ether is selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylmethylcellulose (HEMC), hydroxyethylcellulose (HEC), methylcellulose (MC), and carboxymethylcellulose (CMC). 
     
     
         5 . The dosage form of  claim 4 , wherein the cellulose ether is HPMC. 
     
     
         6 . The dosage form of  claim 1 , wherein the amount of buprenorphine or pharmaceutically acceptable salt thereof is from about 0.1 mg to about 16 mg of buprenorphine. 
     
     
         7 . The dosage form of  claim 6 , wherein the amount of buprenorphine or pharmaceutically acceptable salt thereof is 2 mg, 4 mg, 8 mg, or 16 mg. 
     
     
         8 . The dosage form of  claim 1 , wherein the weight ratio is 2:1 to 8:1. 
     
     
         9 . The dosage form of  claim 8 , wherein the weight ratio is 4:1. 
     
     
         10 . A method of reducing diversion, abuse in drug substitution therapy, or a combination thereof comprising administering to a patient in need thereof the sublingual dosage form of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein the non-gelatin polymeric film-forming material is a modified cellulose material. 
     
     
         12 . The method of  claim 11 , wherein the modified cellulose material is a cellulose ether. 
     
     
         13 . The method of  claim 12 , wherein the cellulose ether is selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylmethylcellulose (HEMC), hydroxyethylcellulose (HEC), methylcellulose (MC), and carboxymethylcellulose (CMC). 
     
     
         14 . The method of  claim 13 , wherein the cellulose ether is HPMC. 
     
     
         15 . The method of  claim 10 , wherein the amount of buprenorphine or pharmaceutically acceptable salt thereof is from about 0.1 mg to about 16 mg of buprenorphine. 
     
     
         16 . The method of  claim 15 , wherein the amount of buprenorphine or pharmaceutically acceptable salt thereof is 2 mg, 4 mg, 8 mg, or 16 mg. 
     
     
         17 . The method of  claim 10 , wherein the ratio is 2:1 to 8:1. 
     
     
         18 . The method of  claim 17 , wherein the ratio is 4:1. 
     
     
         19 . The method of  claim 10 , wherein the amount of the buprenorphine or the pharmaceutically acceptable salt thereof administered via the sublingual dosage form does not exceed 32 mg of buprenorphine per day. 
     
     
         20 . The method of  claim 10 , wherein the sublingual dosage form is placed sublingually. 
     
     
         21 . The dosage form of  claim 1 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is buprenorphine hydrochloride. 
     
     
         22 . The method of  claim 10 , wherein the buprenorphine or pharmaceutically acceptable salt thereof is buprenorphine hydrochloride. 
     
     
         23 . The dosage form of  claim 1 , wherein the buprenorphine or the pharmaceutically acceptable salt thereof is dissolved or homogeneously dispersed in the film. 
     
     
         24 . A sublingual dosage form comprising:
 a. a non-gelatin polymeric film-forming material;   b. an amount of buprenorphine or a pharmaceutically acceptable salt thereof; and   c. an amount of naloxone or a pharmaceutically acceptable salt thereof;   wherein
 the buprenorphine or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in the sublingual dosage form in a weight ratio of from 1:1 to 10:1; 
 the sublingual dosage form releases substantially all of the buprenorphine or pharmaceutically acceptable salt thereof in less than 5 minutes upon sublingual administration; 
 the amount of buprenorphine or pharmaceutically acceptable salt thereof delivered by the sublingual dosage form is from about 0.1 mg to about 16 mg; and 
 the sublingual dosage form is a film.