Sublingual and buccal film compositions

Abstract

The present invention relates to products and methods for treatment of narcotic dependence in a user. The invention more particularly relates to self-supporting dosage forms which provide an active agent for treating narcotic dependence while providing sufficient buccal adhesion of the dosage form.

What is claimed is: 
     
         1 . A method for treating opioid dependence in a patient in need thereof, the method comprising sublingually or buccally administering a mucoadhesive film to a sublingual or buccal mucosal tissue of the patient to treat the opioid dependence;
 wherein the film comprises:   (a) at least 25 wt % of a water-soluble polymeric matrix;   (b) about 2 mg to about 16 mg of buprenorphine or a pharmaceutically acceptable salt thereof and about 0.5 mg to about 4 mg of naloxone or a pharmaceutically acceptable salt thereof; wherein the ratio of the buprenorphine or the pharmaceutically acceptable salt thereof to the naloxone or the pharmaceutically acceptable salt thereof is about 4:1; and   (c) an effective amount of a buffer to achieve a pH in solution substantially equivalent to the pH in solution of a mucoadhesive film comprising about 8 mg buprenorphine, about 2 mg naloxone, about 21.98 mg polyethylene oxide, about 6.02 mg maltitol, about 3.0 mg flavor, about 2.96 mg citric acid, about 2.11 mg hydroxypropylmethyl cellulose, about 1.5 mg acesulfame potassium, about 1.34 mg sodium citrate, and about 0.01 mg colorant.   
     
     
         2 . The method of  claim 1  which provides a buprenorphine C max  from about 0.624 ng/ml to about 5.638 ng/ml; a buprenorphine AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml; a naloxone C max  from about 41.04 pg/ml to about 323.75 pg/ml; and a naloxone AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml. 
     
     
         3 . The method of  claim 1 , wherein the film comprises about 40 wt % to about 60 wt % of the water-soluble polymer matrix. 
     
     
         4 . The method of  claim 1 , wherein the weight ratio of the buprenorphine or the pharmaceutically acceptable salt thereof to the polymeric matrix is from about 1:3 to about 1:11.5. 
     
     
         5 . The method of  claim 1 , wherein the water-soluble polymeric matrix comprises a polyethylene oxide polymer alone or in combination with a hydrophilic cellulosic polymer. 
     
     
         6 . A mucoadhesive film comprising about 8.64 mg buprenorphine hydrochloride, about 2.44 mg naloxone hydrochloride dihydrate, about 21.98 mg polyethylene oxide, about 6.02 mg maltitol, about 3.0 mg flavor, about 2.96 mg citric acid, about 2.11 mg hydroxypropylmethyl cellulose, about 1.5 mg acesulfame potassium, about 1.34 mg sodium citrate, and about 0.01 mg colorant; wherein the film is mucoadhesive to the sublingual mucosa or the buccal mucosa; and wherein the film provides a buprenorphine C max  from about 0.624 ng/ml to about 5.638 ng/ml, a buprenorphine AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml, a naloxone C max  from about 41.04 pg/ml to about 323.75 pg/ml, and a naloxone ACU from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml; or a mucoadhesive film bioequivalent thereto. 
     
     
         7 . The film of  claim 6 , wherein the polyethylene oxide comprises about 13.55 mg polyethylene oxide having a molecular weight of about 200,000; about 6.02 mg polyethylene oxide having a molecular weight of about 100,000; and about 2.41 mg polyethylene oxide having a molecular weight of about 900,000. 
     
     
         8 . A method for treating opioid dependence in a patient in need thereof, the method comprising sublingually or buccally administering the mucoadhesive film of  claim 6  to a sublingual or buccal mucosal tissue of the patient to treat the opioid dependence. 
     
     
         9 . A mucoadhesive film comprising about 12.96 mg buprenorphine hydrochloride, about 3.66 mg naloxone hydrochloride dihydrate, about 32.97 mg polyethylene oxide, about 9.03 mg maltitol, about 4.5 mg flavor, about 4.44 mg citric acid, about 3.16 mg hydroxypropylmethyl cellulose, about 2.25 mg acesulfame potassium, about 2.01 mg sodium citrate, and about 0.02 mg colorant, wherein the film is mucoadhesive to the sublingual mucosa or the buccal mucosa, and wherein the film provides a buprenorphine C max  from about 0.624 ng/ml to about 5.638 ng/ml and a buprenorphine AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml, and a naloxone C max  from about 41.04 pg/ml to about 323.75 pg/ml and a naloxone ACU from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml; or a mucoadhesive film bioequivalent thereto. 
     
     
         10 . A method for treating opioid dependence in a patient in need thereof, the method comprising sublingually or buccally administering the mucoadhesive film of  claim 8  to a sublingual or buccal mucosal tissue of the patient to treat the opioid dependence.