New abuse-resistant pharmaceutical composition for the treatment of opioid dependence

Abstract

There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and/or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency/addiction and/or pain.

1 . A method of treatment of opioid dependency and/or addiction, which method comprises administration of at least one unit dose of a tablet composition to a person suffering from, or susceptible to, opioid dependency and/or addiction, which tablet composition is suitable for sublingual administration and comprises:
 (a) microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof in associative admixture with particles comprising citric acid;   (b) a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof; and   (c) a disintegrant selected from the group croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone and mixtures thereof,   (d) a buprenorphine to naloxone dose ratio in the tablet composition of about 4:1 (calculated as free bases),   (e) a dose of both buprenorphine and naloxone in the tablet composition, which is about 75% of a dose of buprenorphine and naloxone, respectively, present in a random mixture compressed tablet comprising buprenorphine hydrochloride, naloxone hydrochloride dihydrate, lactose monohydrate, mannitol, maize starch, povidone K30, citric acid, sodium citrate, flavoring, acesulfame potassium, and magnesium stearate, wherein the random mixture compressed tablet was approved under NDA No. 20-733 in 2 mg and 8 mg buprenorphine doses on Oct. 8, 2002 and   which method achieves, after an initial administration of said unit dose of said tablet composition, plasma-concentration time profiles for both buprenorphine and naloxone that are essentially equivalent to plasma-concentration time profiles for buprenorphine and naloxone, respectively, exhibited by said random mixture compressed tablet, where the plasma-concentration time profiles are measured as (i) a maximum plasma concentration (C max ), (ii) total area under the plasma concentration-time curve from time zero to the time of a last measured plasma concentration (AUC t ), or (iii) area under the plasma concentration-time curve from time zero to a last measured plasma concentration extrapolated to infinity based on an elimination rate constant (AUC inf ).   
     
     
         2 . A method according to  claim 1 , wherein the microparticles of buprenorphine or salt thereof have a weight based mean diameter of less than about 15 μm. 
     
     
         3 . A method according to  claim 2  wherein the microparticles of buprenorphine or salt thereof and carrier particles are present in the form of an interactive mixture whereby the microparticles of buprenorphine or salt thereof are presented upon the surfaces of the carrier particles. 
     
     
         4 . A method according to  claim 1  wherein the microparticles of buprenorphine or salt thereof and carrier particles are present in the form of an interactive mixture whereby the microparticles of buprenorphine or salt thereof are presented upon the surfaces of the carrier particles. 
     
     
         5 . A method according to  claim 3  or  4 , wherein the carrier particles are of a size between about 100 and about 800 μm. 
     
     
         6 . A method according to  claim 3  or  4 , wherein the carrier particles are water-soluble. 
     
     
         7 . A method according to  claim 5 , wherein the carrier particles are water-soluble. 
     
     
         8 . A method according to  claim 3  or  4 , wherein the carrier particles comprise mannitol. 
     
     
         9 . A method according to  claim 3  or  4 , wherein the carrier particles comprise the particles of citric acid. 
     
     
         10 . A method according to  claim 1 ,  2 ,  3 , or  4 , wherein the tablet composition comprises particles comprising the naloxone or salt thereof and the disintegrant. 
     
     
         11 . A method according to  claim 1 , wherein the citric acid is present in an amount that enables the provision, when the tablet composition is dissolved in water or saliva, of a pH of between about 4.0 and about 6.25, and the maintenance of pH within that range for up to about 3 minutes.