Dosage Form

• US 20130330409A1
• Filed: 12/09/2011
• Published: 12/12/2013
• Est. Priority Date: 12/09/2010
• Status: Abandoned Application

• Current Assignee: Euroceltique SA
• Original Assignee: Euroceltique SA
• Inventors: Mohammad, Hassan
• Application Number:
  US13/992,946
• Publication Number:
  US 20130330409A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• 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 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• 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
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: B29B 9/12 characterised by structure or composition

Abstract

The present invention provides a dosage form, particularly a tamper resistant dosage form, comprising; non-stretched melt extruded particulates comprising a drug selected from an opioid agonist, a tranquilizer, a CNS depressant, a CNS stimulant or a sedative hypnotic; and a matrix; wherein said melt extruded particulates are present as a discontinuous phase in said matrix.

Claims

1. A dosage form comprising:

non-stretched, melt-extruded particulates comprising a drug selected from an opioid agonist, a tranquilizer, a CNS depressant, a CNS stimulant or a sedative hypnotic; and

a matrix;

wherein said melt-extruded particulates are present as a discontinuous phase in said matrix.

2. The dosage form as claimed in claim 1, wherein said drug is an opioid agonist.

3. The dosage form as claimed in claim 2, wherein said opioid agonist is selected from the group consisting of oxycodone, oxymorphone, hydrocodone, hydromorphone, morphine, codeine, buprenorphine, fentanyl, tramadol, and tapentadol, or a pharmaceutically acceptable salt thereof.

4. The dosage form as claimed in claim 1, which comprises 15-80% wt of said melt-extruded particulates, based on the total weight of the dosage form.

5. The dosage form as claimed in claim 1, which comprises 20-85% wt of said matrix, based on the total weight of the dosage form.

6. The dosage form as claimed in claim 1, wherein said matrix comprises a continuous phase comprising a gel-forming agent.

7. The dosage form as claimed in claim 1 in the form of a tablet.

11. The dosage form as claimed in claim 1, wherein said melt-extruded particulates are microparticulates.

12. The dosage form as claimed in claim 1, wherein said melt-extruded particulates have a diameter and/or length of less than about 900 μ

m.

14. The dosage form as claimed in claim 1, wherein said melt-extruded particulates comprise 3 to 50% wt of drug, based on the total weight of a particulate.

16. The dosage form as claimed in claim 1, wherein said melt-extruded particulates further comprise a polymer conferring crush resistance.

17. The dosage form as claimed in claim 1, wherein said melt-extruded particulates further comprise a polymer selected from an acrylic polymer, a methacrylic polymer or a mixture thereof.

18. The dosage form as claimed in claim 17, wherein said polymer is selected from the group consisting of an acrylic acid and methacrylic acid copolymer, a methyl methacrylate copolymer, ethoxyethyl methacrylate, cyanoethyl methacrylate, poly(acrylic acid), poly(methacrylic acid), a methacrylic acid alkylamide copolymer, poly(methyl methacrylate), polymethacrylate, a poly(methyl methacrylate) copolymer, polyacrylamide, a aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and a glycidyl methacrylate copolymer.

19. The dosage form as claimed in claim 18, wherein said acrylic acid and methacrylic acid copolymer is selected from acrylic acid alkyl esters, methacrylic acid alkyl esters and mixtures thereof.

21. The dosage form as claimed in claim 1, wherein said melt-extruded particulates further comprise a rate controlling or modifying agent.

22. The dosage form as claimed in claim 21, wherein said rate controlling or modifying agent is an alkyl cellulose.

24. The dosage form as claimed in claim 1, wherein said melt-extruded particulates further comprise a lubricant.

25. The dosage form as claimed in claim 1, wherein said melt-extruded particulates further comprise a plasticiser.

26. The dosage form as claimed in claim 1, wherein said melt-extruded particulates comprise oxycodone or hydromorphone, or a hydrochloride salt thereof, an ethyl acrylate and methyl methacrylate copolymer, ethyl cellulose as a rate controlling or modifying agent, stearyl alcohol and/or triethyl citrate as a plasticiser, glyceryl dibehenate as a lubricant and optionally an opioid antagonist.

27. The dosage form as claimed in claim 1, wherein said melt-extruded particulates comprise an opioid agonist and further comprise an opioid antagonist.

28. The dosage form as claimed in claim 1, wherein said melt-extruded particulates are spherical or near spherical.

29. The dosage form as claimed in claim 1, wherein said matrix comprises a silicone and/or a gel-forming agent.

30. The dosage form as claimed in claim 29, wherein said gel-forming agent is selected from polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose, carbomers, poly(uronic) acids or mixtures thereof.

31. The dosage form as claimed in claim 29, wherein said silicone or gel-forming agent is curable.

52. A method of treating a subject in need of pain relief, comprising administering to said subject a dosage form as claimed in claim 1.

53. The dosage form as claimed in claim 26, wherein said melt-extruded particulates comprise oxycodone hydrochloride salt or hydromorphone hydrochloride salt.

54. The dosage form as claimed in claim 26, wherein said ethyl acrylate and methyl methacrylate copolymer is Eudragit NE 30 D or NE 40 D.

55. The dosage form as claimed in claim 27, wherein said opioid antagonist is naloxone.

8-10. -10. (canceled)

13. (canceled)

15. (canceled)

20. (canceled)

23. (canceled)

32. (canceled)

33. A process for preparing a dosage form comprising a drug selected from an opioid agonist, a tranquilizer, a CNS depressant, a CNS stimulant or a sedative hypnotic comprising:

i) melt extruding a composition comprising the drug through extrusion die head orifices of less than 1.0 mm in diameter to form a melt extrudate having an average diameter of less than about 1000 μ

m;

ii) cutting the melt extrudate to form particulates having an average diameter of less than about 1000 μ

m;

iii) mixing said particulates with a matrix material so that said particulates form a discontinuous phase in said matrix; and

iv) forming said mixture into a dosage form.

34. The process as claimed in claim 33, further comprising a step of stretching said melt extrudate to form a stretched melt extrudate prior to cutting.

35. The process as claimed in claim 33, wherein in said cutting step a cutter cuts the melt extrudate as it emerges under pressure and still softened from the orifices of the die plate.

38. The process as claimed in claim 33, wherein said particulates are melt extruded at a temperature of 100°

C. or less.

39. The process as claimed in claim 33, comprising a further step of curing said matrix.

36-37. -37. (canceled)

40-51. -51. (canceled)