PROCESS FOR PREPARING PARTICLES OF OPIOIDS AND COMPOSITIONS PRODUCED THEREBY

• US 20100183687A1
• Filed: 01/22/2010
• Published: 07/22/2010
• Est. Priority Date: 01/22/2009
• Status: Abandoned Application

• Current Assignee: Cox D. Phillip, James D. Talton
• Original Assignee: Cox D. Phillip, James D. Talton
• Inventors: Cox, D. Phillip, Talton, James D.
• Application Number:
  US12/692,170
• Publication Number:
  US 20100183687A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

Abstract

The present invention provides compositions comprising particles comprising a poorly soluble opioid drug and a stabilizer, wherein the particles have an average diameter of less than about 10,000 nm. Methods of making the compositions and their use as pharmaceutical compositions for treating disorders such as pain are also described.

Claims

1. A composition comprising particles comprising a poorly soluble opioid drug and a stabilizer, wherein the particles have an average diameter of less than about 10,000 nm.

2. The composition of claim 1, wherein the poorly soluble opioid drug includes naturally-occurring, synthetic, and semi-synthetic opioids.

3. The composition of claim 2, wherein the poorly soluble opioid drug is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonidine, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazine, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levomethadyl, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylnaltrexone bromide, metopon, morphine, myrophine, nalbuphine, naloxone, naltrexone, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, remifentanil, sulfentanil, tramadol, and tilidine, or pharmaceutically acceptable salts thereof.

4. The composition of claim 3, wherein the poorly soluble opioid drug is oxycodone or a pharmaceutically acceptable salt thereof.

5. The composition of claim 1, wherein the particles comprise a poorly soluble opioid drug encapsulated by the stabilizer.

6. The composition of claim 5, wherein the stabilizer is poly-vinyl-pyrollidone.

7. The composition of claim 1, wherein the particles have an average diameter of less than about 1000 nm.

8. The composition of claim 1, wherein the particles have an average diameter of less than about 550 nm.

9. The composition of claim 4, wherein the oxycodone content ranges from about 10% to about 90%.

10. The composition of claim 1, wherein said composition further comprise at least one excipient.

11. A method of making the composition of claim 1, the method comprising:

blending a poorly soluble opioid drug together with a stabilizer to form a mixture;

processing said mixture to form coarse particles having an average diameter ranging from about 0.1 mm to about 5 mm; and

processing said coarse particles to form fine particles having an average diameter ranging from about 100 nanometers to about 10,000 nanometers.

12. The method of claim 11, wherein the mixture of the poorly soluble opioid drug and the stabilizer are processed by mixing or granulating to form the coarse particles.

13. The method of claim 12, wherein the coarse particles are processed by jet-milling to form the fine particles.

14. The method of claim 11, wherein the fine particles are milled to an average diameter of less than about 1000 nm.

15. The method of claim 11, wherein the fine particles are milled to an average diameter of less than about 550 nm.

16. The method of claim 11, wherein the fine particles comprise the poorly soluble opioid drug encapsulated by the stabilizer.

17. The method of claim 13, wherein the poorly soluble opioid drug is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonidine, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazine, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levomethadyl, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylnaltrexone bromide, metopon, morphine, myrophine, nalbuphine, naloxone, naltrexone, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, remifentanil, sulfentanil, tramadol, and tilidine, or pharmaceutically acceptable salts thereof.

18. The method of claim 17, wherein the poorly soluble opioid drug is oxycodone or pharmaceutically acceptable salts thereof.

19. The method of claim 13, wherein the stabilizer is poly-vinyl-pyrollidone.

20. A method of treating pain comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 1.

21. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.