CRYSTALS OF LAQUINIMOD SODIUM, AND PROCESS FOR THE MANUFACTURE THEREOF

• US 20110118308A1
• Filed: 01/21/2011
• Published: 05/19/2011
• Est. Priority Date: 10/19/2005
• Status: Active Grant

• Current Assignee: Teva Pharmaceutical Industries Limited
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Gurevich, Eduard, Frenkel, Anton, Laxer, Avital
• Granted Patent: US 8,673,322 B2
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/54 attached in position 3
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4

Abstract

Disclosed is a process for the preparation of laquinimod sodium which removes the impurities after the salt formation step, thus resulting in crystals of higher purity as well as crystals having improved crystalline characteristics.

Claims

1-40. -40. (canceled)

41. A mixture of crystalline laquinimod sodium particles, having a bulk density of at least 0.2 g/mL.

42. The mixture of claim 41, having a tapped density of at least 0.4 g/mL.

43. The mixture of claim 42, having a tapped density of at least 0.5 g/mL.

44. The mixture of claim 41, having a tapped density of less than 0.7 g/mL.

45. The mixture of claim 41, having a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

46. The mixture of claim 45, having a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

47. The mixture of claim 41, having a bulk density of at least 0.3 g/mL.

48. The mixture of claim 47, having a tapped density of at least 0.4 g/mL.

49. The mixture of claim 48, having a tapped density of at least 0.5 g/mL.

50. The mixture of claim 47, having a tapped density of less than 0.7 g/mL.

51. The mixture of claim 47, having a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

52. The mixture of claim 51, having a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

53. The mixture of claim 41, comprising no more than 2 ppm of a heavy metal.

54. The mixture of claim 45, comprising no more than 2 ppm of a heavy metal.

55. The mixture of claim 46, comprising no more than 2 ppm of a heavy metal.

56. The mixture of claim 47, comprising no more than 2 ppm of a heavy metal.

57. The mixture of claim 51, comprising no more than 2 ppm of a heavy metal.

58. The mixture of claim 52, comprising no more than 2 ppm of a heavy metal.

59. The mixture of claim 53, wherein the heavy metal is iron, nickel or chromium.

60. The mixture of claim 54, wherein the heavy metal is iron, nickel or chromium.

61. The mixture of claim 55, wherein the heavy metal is iron, nickel or chromium.

62. The mixture of claim 56, wherein the heavy metal is iron, nickel or chromium.

63. The mixture of claim 57, wherein the heavy metal is iron, nickel or chromium.

64. The mixture of claim 58, wherein the heavy metal is iron, nickel or chromium.

65. A pharmaceutical composition comprising the mixture of claim 41 and a pharmaceutically acceptable carrier.

66. the pharmaceutical composition of claim 65, wherein the mixture has a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

67. the pharmaceutical composition of claim 66, wherein the mixture has a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

68. the pharmaceutical composition of claim 65, wherein the mixture has a bulk density of at least 0.3 g/mL.

69. the pharmaceutical composition of claim 68, wherein the mixture has a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

70. the pharmaceutical composition of claim 69, wherein the mixture has a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

71. The pharmaceutical composition of claim 65 in the form of a tablet or capsule.

72. the pharmaceutical composition of claim 71, wherein the mixture has a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

73. the pharmaceutical composition of claim 72, wherein the mixture has a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

74. the pharmaceutical composition of claim 71, wherein the mixture has a bulk density of at least 0.3 g/mL.

75. the pharmaceutical composition of claim 74, wherein the mixture has a tapped density of at least 0.5 g/mL and less than 0.7 g/mL.

76. the pharmaceutical composition of claim 75, wherein the mixture has a tapped density of at least 0.6 g/mL and less than 0.7 g/mL.

77. A composition comprising laquinimod sodium and no more than 2 ppm of a heavy metal calculated based on total amount of laquinimod sodium in the composition.

78. The composition of claim 77, wherein the heavy metal is iron, nickel or chromium.

79. The composition of claim 78, wherein the iron content is no more than 2 ppm.

80. The composition of claim 78, wherein the nickel content is no more than 0.2 ppm.

81. The composition of claim 78, wherein the chromium content is no more than 0.3 ppm.

82. The composition of claim 77 in crystalline form.

83. The composition of claim 77 further comprising a pharmaceutically acceptable carrier.

84. The composition of claim 77 in the form of a tablet or capsule.