Stable pharmaceutical compositions for 2-aza-bicyclo [3.30]-octane-3-carboxylic acid derivatives

• US 20070212409A1
• Filed: 05/10/2007
• Published: 09/13/2007
• Est. Priority Date: 06/26/2003
• Status: Abandoned Application

• Current Assignee: Julia Hrakovshy, Ruth Tenengauzer
• Original Assignee: Julia Hrakovshy, Ruth Tenengauzer
• Inventors: Tenengauzer, Ruth, Hrakovshy, Julia
• Application Number:
  US11/801,777
• Publication Number:
  US 20070212409A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A stable composition of a 2-aza-bicyclo[3.3.0]-octane-3-carboxylic acid derivative and a method for its preparation are described. The stable composition includes an intimate admixture of the derivative and a stabilizing effective amount of a lubricant. The stable composition further includes an external excipient. A method of preparing the stable composition includes forming an intimate admixture of the derivative and a lubricant and then blending the intimate admixture with at least one excipient. Preferably the final blend is transformed into solid unit dosage form.

Claims

1-38. -38. (canceled)

39. A pharmaceutical composition comprising ramipril comilled with a lubricant selected from the group consisting of glyceryl behenate, polyethylene glycol, stearic acid, sodium stearyl fumarate, and combinations thereof.

40. The composition of claim 39, wherein the lubricant is about 0.3% to about 60% by weight of the comilled component.

41. The composition of claim 39, wherein the lubricant is about 0.8% to about 50% by weight of the comilled component.

42. The composition of claim 39, wherein the lubricant is about 1% to about 40% by weight of the comilled component.

43. The composition of claim 39, wherein the lubricant is about 2% to about 10% by weight of the comilled component.

44. The composition of claim 39, wherein the lubricant is about 2% by weight of the comilled component.

45. The composition of claim 39, wherein the lubricant is about 44% by weight of the comilled component.

46. The composition of claim 39, wherein the ramipril is substantially stable against decomposition into a degradant product.

47. The composition of claim 39, wherein the degradant product is ramipril-diacid or ramipril-diketopiperazine.

48. The composition of claim 39, wherein the composition is a solid dosage form.

49. The composition of claim 39, wherein the composition is an oral dosage form.

50. The composition of claim 39, wherein the composition is a tablet, caplet or capsule.

51. The composition of claim 39, wherein the composition is a tablet.

52. The composition of claim 39, wherein the composition further comprises an excipient.

53. The composition of claim 39, wherein the ramipril is between the amount of about 0.3% to about 6% by weight of the total composition.

54. The composition of claim 39, wherein the ramipril is in an amount of about 1.25 mg.

71. A method of treating a cardiovascular disorder comprising administering a composition according to claim 39.

73. The method of claim 71, wherein the cardiovascular disorder is hypertension.

55. A method of making a pharmaceutical composition comprising co-milling ramipril with a lubricant selected from the group consisting of glyceryl behenate, polyethylene glycol, stearic acid, sodium stearyl fumarate, and combinations thereof.

56. The method of claim 55, further comprising adding a diluent, lubricant, disintegrant or a combination thereof.

57. The method of claim 55, further comprising compressing the comilled component into tablet form.

58. The method of claim 55, wherein the lubricant is about 0.3% to about 60% by weight of the comilled component

59. The method of claim 55, wherein the lubricant is about 0.8% to about 50% by weight of the comilled component

60. The method of claim 55, wherein the lubricant is about 1% to about 40% by weight of the comilled component.

61. The method of claim 55, wherein the lubricant is about 2% to about 10% by weight of the comilled component.

62. The method of claim 55, wherein the lubricant is about 2% by weight of the comilled component.

63. The method of claim 55, wherein the lubricant is about 44% by weight of the comilled component.

64. The method of claim 55, wherein the composition is a solid dosage form.

65. The method of claim 55, wherein the composition is an oral dosage form.

66. The method of claim 55, wherein the composition is a tablet, caplet or capsule.

67. The method of claim 55, wherein the composition is a tablet.

68. The method of claim 55, wherein the ramipril is in the amount of about 0.3% to about 6% by weight of the total composition.

69. The method of claim 55, wherein the ramipril is in an amount of about 1.25 mg.

70. A composition prepared according to the method of claim 55.

72. A method of treating a cardiovascular disorder comprising administering a composition according to claim 55.

74. The method of claim 72, wherein the cardiovascular disorder is hypertension.