Abuse-resistant pharmaceutical composition for the treatment of opioid dependence
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 process for making a tablet comprising buprenorphine or pharmaceutically-acceptable salt thereof and naloxone or a pharmaceutically-acceptable salt thereof, which process comprises:
(a) associatively admixing microparticles of said buprenorphine or pharmaceutically-acceptable salt thereof with particles of citric acid by a process of simple mixing and/or dry granulation, to form an associative admixture between the microparticles of buprenorphine or salt thereof and the particles of citric acid;
(b) mixing the associative admixture obtained in step (a) with a disintegrant and particles comprising said naloxone or pharmaceutically-acceptable salt thereof; and
(c) compressing the mixture obtained in step (b) to produce said tablet.
2 . The process as claimed in claim 1 , wherein a dosage amount of buprenorphine or pharmaceutically-acceptable salt thereof (calculated as the free base) in the tablet is 11.4 mg (±2%), 8.6 mg (±2%), 5.7 mg (±2%), 2.9 mg (±2%), or 1.4 mg (±2%); and wherein a dosage amount of naloxone or pharmaceutically-acceptable salt thereof (calculated as the free base) is about ¼ of the respective doses of buprenorphine or salt thereof.
3 . The process as claimed in claim 1 , wherein the disintegrant is selected from the group croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone, and mixtures thereof.
4 . The process as claimed in claim 1 , which further comprises associatively admixing sodium citrate with said citric acid and said buprenorphine or pharmaceutically-acceptable salt thereof in step (a) by the process of simple mixing and/or dry granulation.
5 . The process as claimed in claim 1 , which further comprises associatively admixing carrier particles with said citric acid and said buprenorphine or pharmaceutically-acceptable salt thereof in step (a) by the process of simple mixing and/or dry granulation.
6 . The process as claimed in claim 1 , wherein the associative admixing in step (a) comprises simple mixing.
7 . The process as claimed in claim 1 , wherein the associative admixing in step (a) comprises dry granulation.
8 . The process as claimed in claim 1 , which further comprises admixing a binder with the associative admixture obtained in step (a).
9 . The process as claimed in claim 8 , wherein the binder is a cellulose gum or microcrystalline cellulose.
10 . The process as claimed in claim 1 , wherein the disintegrant and particles comprising said naloxone or pharmaceutically-acceptable salt thereof are mixed together prior to said mixing with the associative admixture obtained in step (a).