Injectable methadone, methadone and naltrexone, or buprenorphine and naltrexone microparticle compositions and their use in reducing consumption of abused substances
View Patent ↗An injectable slow-release methadone, partial opioid agonist or opioid antagonist formulation is provided comprising methadone, a partial opioid agonist or opioid antagonist in a poly(D,L-lactide) excipient with a small amount of residual ethyl acetate. Upon intramuscular or subcutaneous injection of the composition, methadone, a partial opioid agonist or opioid antagonist is released in a controlled manner over an extended period of time. The composition finds use in the treatment of heroin addicts and alcoholics to reduce consumption of the abused substances. Of particular interest are the drugs buprenorphine, methadone and naltrexone.
1. A slow release formulation comprising:
a mixture of a first population of microspheres and a second population of microspheres, wherein said first population comprises a buprenorphine and a residual amount of ethyl acetate that is from about 0.1 to about 3 weight %, and said second population comprises an naltrexone and a residual amount of ethyl acetate that is less than about 3 weight % ethyl acetate, and wherein said mixture provides a therapeutically effective dose of medication for the treatment of at least one of heroin and alcohol abuse for a period of at least 28 days when said slow release formulation is introduced into a mammal.
2. A microparticle composition comprising methadone in an amount in the range of 10 to 70 weight %, poly(D,L-lactide) as an excipient, and a residual amount of ethyl acetate that is from about 0.1 to about 3 weight %, capable of providing a physiologically effective plasma level over a period of at least about 28 days of said methadone to reduce the consumption of at least one of heroin and alcohol when administered intramuscularly or subcutaneously in a mammal, at least 90 weight % of said microparticle composition comprising microparticles having a diameter in the range of 20 to 125 μm.
3. The microparticle composition according to claim 2 , wherein said methadone is present in an amount in the range of 15 to 50 weight%, and said poly(D,L-lactide) has an inherent viscosity in the range of about 0.3 to 0.4 dL/g.
4. The microparticle composition according to claim 2 , wherein said methadone is present in an amount in the range of 30 to 65 weight %, and said poly(D,L-lactide) has an inherent viscosity in the range of about 1.0 to 1.1 dL/g.
5. The microparticle composition according to claim 2 , wherein said poly(D,L-lactide) is a mixture of poly(D,L-lactide)s of differing inherent viscosities.
6. The microparticle composition according to claim 2 , wherein said composition is a mixture of microparticles which differ in at least one of weight % of said methadone or poly(D,L-lactide)s of differing inherent viscosities.
7. The microparticle composition according to claim 2 , wherein said microparticles are prepared by introducing a solution of said methadone and poly(D,L-lactide) in ethyl acetate into an aqueous ethyl acetate containing solution of poly(vinyl alcohol) to form an emulsion and adding said emulsion to water to extract ethyl acetate to form microparticles, and isolating the resulting microparticles.
8. A formulation for injection comprising a microparticle composition according to claim 2 , carboxymethyl cellulose, Tween and mannitol.
9. A method for reducing the consumption of heroin and/or alcohol by a subject abusing at least one of heroin and alcohol, said method comprising:
administering intramuscularly or subcutaneously an effective dose of a microparticle composition according to claim 2 in an amount to inhibit the consumption of heroin and alcohol, whereby the consumption of heroin and/or alcohol is reduced.
10. A method for reducing the consumption of heroin and alcohol by a subject abusing at least one of heroin and alcohol, said method comprising:
administering an effective dose of a microparticle composition according to claim 2 , which composition continues to release said methadone for a period greater than 28 days at at least an effective dose;
prior to the level of said methadone falling below an effective dose, administering a second dose of said microparticle composition, whereby the combination of said original effective dose and said second dose provide an effective dose of said methadone for a second period of at least an additional 28 days; and
repeating said administration to have said methadone being released from both a prior administration of said microparticle composition and the lately administered microparticle composition to maintain said effective dose of said methadone.
11. The method according to claim 10 , wherein at least one of said period and said second period is about 60 days.
12. A slow release formulation comprising:
a mixture of a first population of microspheres and a second population of microspheres, wherein said first population comprises methadone and a residual amount of ethyl acetate that is from about 0.1 to about 3 weight %, and said second population comprises an opioid antagonist and a residual amount of ethyl acetate that is from about 0.1 to about 3 weight %, and wherein said mixture provides a therapeutically effective dose of medication for the treatment of at least one heroin and alcohol abuse for a period of at least 28 days when said slow release formulation is introduced into a mammal.