Therapeutic agents

• US 20040219220A1
• Filed: 06/08/2004
• Published: 11/04/2004
• Est. Priority Date: 06/07/2001
• Status: Abandoned Application

• Current Assignee: Reckitt Benckiser Healthcare UK Ltd (Reckitt Benckiser Group PLC)
• Original Assignee: Boots Healthcare International Ltd (Reckitt Benckiser Group PLC)
• Inventors: Sherry, Robert Arthur, Edinborough, Nicholas David, Dring, Richard James
• Application Number:
  US10/479,424
• Publication Number:
  US 20040219220A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: B01J 2/20 by expressing the material, e.g. through sieves and fragmenting the extruded length
• CPC Class Codes: B29C 48/40 using two or more parallel screws or at least two parallel non-intermeshing screws, e.g. twin screw extruders
• CPC Class Codes: B29C 48/41 Intermeshing counter-rotating screws
• CPC Class Codes: B29C 48/57 provided with kneading disc-like elements, e.g. with oval-shaped elements

Abstract

A process for the preparation of a granular composition comprising solidified melt granules comprising a non-steroidal anti-inflammatory drug (NSAID) as a continuous phase, which process comprising the steps of: (a) melt-extruding the NSAID, optionally with excipients; (b) forming a homogeneous extrudate; (c) cooling the extrudate; and (d) comminuting the cooled extrudate to form granules; characterised in that in the step (a) the NSAID is fully melted and that in step (b) the extrudate is formed into two or more ribbons having a depth of 10 mm or less and which solidify in 5 minutes or less.

Claims

1-25. -25. (Cancelled)

26. A process for the preparation of a granular composition comprising solidified melt granules comprising a non-steroidal anti-inflammatory drug (NSAID) as a continuous phase, which process comprising the steps of:

(a) melt-extruding the NSAID, optionally with excipients;

(b) forming a homogeneous extrudate;

(c) cooling the extrudate; and

(d) comminuting the cooled extrudate to form granules;

characterised in that in step (a) the NSAID is fully melted and that in step (b) the extrudate is formed into two or more ribbons having a depth of 10 mm or less and which solidify in 5 minute or less.

27. A process according to claim 26, wherein the NSAID has a melting point of from 30 to 300°

C.

28. A process according to claim 26, wherein the ribbons of molten extrudate are cooled in 3 minutes or less.

29. A process according to claim 26, wherein step (c) takes place on a cooling means selected from a cooling belt and a cooling drum.

30. A process according to claim 26, wherein the width of each ribbon of molten extrudate is greater that the depth of the ribbon.

31. A process according to claim 26, wherein the ribbons of molten extrudate solidify in 1 minute or less.

32. A process according to claim 26, wherein each ribbon of molten extrudate has a depth of up to 6 mm.

33. A process according to claim 26, wherein each ribbon of molten extrudate has a depth of 0.5-4 mm.

34. A process according to claim 26, wherein each ribbon of molten extrudate has a depth of 1-3 mm.

35. A process according to claim 26, wherein three or more ribbons of molten extrudate are formed.

36. A process according to claim 29, wherein the temperature difference between said molten extrudate and the cooling means as it comes into contact with cooling means is at least 50°

C.

37. A process according to claim 26, wherein the extruder is heated to a temperature above the melting point of the NSAID.

38. A process according to claim 26, wherein the NSAID is ibuprofen, flurbiprofen, ketoprofen, naproxen or an enantiomer or a salt thereof.

39. A process according to claim 38, wherein the NSAID is racemic ibuprofen or S(+)-ibuprofen.

40. A process according to claim 26, wherein a disintegrant is melt-extruded with the NSAID.

41. A process according to claim 40, wherein the ratio of NSAID to disintegrant is 10:

1 to 1;

10 parts by weight.

42. A process according to claim 26, wherein step (a) is carried out in an extruder having at least one screw shaft provided with means arranged to generate heat within the NSAID.

43. A process according to claim 26 in which a twin-screw extruder is employed.

44. A process according to claim 42 wherein the extruder comprises an extruder barrel heated to a temperature in the range 80-130°

C.

45. A process according to claim 26, wherein the NSAID is fully molten as it exits the extruder.

46. A process according to claim 26, wherein the solid composition collected is milled through a screen having a round hole size of less than 2 mm.

47. An apparatus suitable for use in the method of claim 26, comprising a feeder hopper, an extruder with an endplate mounted thereon, a cooling belt and a collection hopper, wherein the endplate comprises a plurality of channels which in use divide molten extrudate into a plurality of streams.

48. An apparatus according to claim 47, wherein the extruder comprises an extruder barrel, twin screw shafts, a powder inlet, a transfer zone enclosed by a water cooled jacket, a heated mixing zone enclosed by a thermal jacket and an extruder outlet.

49. An apparatus according to claim 47, wherein the cooling belt is a continuously rotating stainless steel cooling belt which is water cooled along its entire length.

50. An apparatus according to claim 47, wherein the end plate comprises from 2 to 10 channels.

51. An apparatus according to claim 48, wherein the end plate comprises from 2 to 10 channels.