SUSTAINED-RELEASE TABLET COMPOSITION

• US 20090143387A1
• Filed: 12/19/2008
• Published: 06/04/2009
• Est. Priority Date: 07/25/2002
• Status: Abandoned Application

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Reo, Joseph P., Ganorkar, Loksidh D., Amidon, Gregory E., Lee, Ernest J., Heimlich, John M., Skoug, Connie J., Noack, Robert M., Martino, Alice C.
• Application Number:
  US12/339,212
• Publication Number:
  US 20090143387A1
• Time in Patent Office: Days
• US Class Current: 514/239.200
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence

Abstract

A sustained-release pharmaceutical composition in a form of an orally deliverable tablet containing reboxetine, or a pharmaceutically acceptable salt thereof, dispersed in a matrix containing a hydrophilic polymer and a starch, wherein the starch has a tensile strength of at least 0.15 kN cm⁻² at a solid fraction of 0.75 to 0.85.

Claims

1-37. -37. (canceled)

38. A pharmaceutical composition in a form of an orally deliverable tablet comprising reboxetine, or a pharmaceutically acceptable salt thereof, dispersed in a matrix comprising a hydrophilic polymer and a starch, wherein the starch has a tensile strength of at least 0.15 kN cm⁻

2 at a solid fraction of 0.75 to 0.85.

39. The composition of claim 38 wherein the starch has a tensile strength of at least 0.175 kN cm⁻

2 at a solid fraction of 0.75 to 0.85.

40. The composition of claim 38 wherein the starch has a tensile strength of at least 0.2 kN cm⁻

2 at a solid fraction of 0.75 to 0.85.

41. The composition of claim 38 wherein the starch is a pregelatinized starch.

42. The composition of claim 38 wherein the starch is present in an amount of about 25% to about 75% by weight of the tablet.

43. The composition of claim 38 wherein the starch is present in an amount of about 40% to about 70% by weight of the tablet.

44. The composition of claim 38 wherein the starch is present in an amount of about 45% to about 65% by weight of the tablet.

45. The composition of claim 38 wherein the hydrophilic polymer is selected from the group consisting of methylcellulose, hydroxypropylmethylcellulose, carmellose sodium and carbomer.

46. The composition of claim 38 wherein the hydrophilic polymer is hydroxypropylmethylcellulose.

47. The composition of claim 38 wherein the hydrophilic polymer is present in an amount of about 20% to about 70% by weight of the tablet.

48. The composition of claim 38 wherein the hydrophilic polymer is present in an amount of about 30% to about 60% by weight of the tablet.

49. The composition of claim 38 wherein the hydrophilic polymer is present in an amount of about 35% to about 50% by weight of the tablet.

50. The composition of claim 38 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

51. The composition of claim 50 wherein the (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine succinate.

52. The composition of claim 38 that comprises 0.2 to 15 mg reboxetine per tablet.

53. The composition of claim 38 that comprises 1 to 12 mg reboxetine per tablet.

54. The composition of claim 38, further comprising a coating on the tablet.

55. The composition of claim 54 wherein said coating is a release-controlling layer.

56. The composition of claim 55 wherein said release-controlling layer constitutes 1% to 15% by weight of the tablet.

57. The composition of claim 54 wherein said coating is a nonfunctional coating.

59. A method of treatment of a subject having a central nervous system condition or disorder for which reboxetine, or a pharmaceutically acceptable salt thereof, is indicated, wherein:

the method comprises orally administering to the subject the pharmaceutical composition of claim 38.

60. The method of claim 59 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine succinate.

61. A process for preparing a pharmaceutical composition according to claim 38 in a form of an orally deliverable, sustained-release tablet, the process comprising selecting by a suitable test a starch having a tensile strength of at least 0.15 kN cm⁻

2 at a solid fraction of 0.75 to 0.85;

admixing with the selected starch a hydrophilic polymer and reboxetine, or a pharmaceutically acceptable salt thereof, to provide a mixture wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is dispersed in a matrix comprising the polymer and the starch; and

compressing the mixture to form said tablet.

62. The composition of claim 39 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

63. The composition of claim 40 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

64. The composition of claim 41 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

65. The composition of claim 42 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

66. The composition of claim 43 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

67. The composition of claim 44 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

68. The composition of claim 45 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

69. The composition of claim 46 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

70. The composition of claim 47 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

71. The composition of claim 48 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

72. The composition of claim 49 wherein the reboxetine, or a pharmaceutically acceptable salt thereof, is (S,S)-reboxetine, or a pharmaceutically acceptable salt thereof.

58. A pharmaceutical composition in a form of an orally deliverable tablet, comprising (S,S)-reboxetine succinate dispersed in a matrix comprising (a) HPMC in an amount of 35% to 50% by weight of the tablet and (b) a pregelatinized starch having a tensile strength of at least 0.15 kN cm⁻

2 at a solid fraction of 0.8, in an amount of 45% to 65% by weight of the tablet.