Forms of pravastatin sodium

• US 7,001,919 B2
• Filed: 12/14/2000
• Issued: 02/21/2006
• Est. Priority Date: 12/14/1999
• Status: Expired due to Fees

• Current Assignee: Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Gyogyszergyar Reszvenytarsasag
• Inventors: Aronhime, Judith, Szabo, Csaba, Keri, Vilmos, Arvai, Edit Nagyne
• Primary Examiner(s): Zucker, Paul A.
• Application Number:
  US09/736,796
• Publication Number:
  US 20010041809A1
• Time in Patent Office: 1,895 Days
• Field of Search: 560/248, 560/256, 514/548
• US Class Current: 514/548
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 2602/28 Hydrogenated naphthalenes
• CPC Class Codes: C07C 67/52 by change in the physical state, e.g. crystallisation
• CPC Class Codes: C07C 69/33 esterified with hydroxy compounds having more than three hydroxy groups esters of sugars C07H

Abstract

New polymorphic forms of pravastatin sodium are provided. Each of the new forms is selectively obtained by crystallization from different solvent systems, each solvent system having a protic component, and by controlling the rate of crystallization through temperature. The new polymorphic forms are suitable for use as active substances of pharmaceutical dosage forms for reduction of serum cholesterol levels in the bloodstream.

Claims

1. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 3.9, 4.5, 6.2, 7.2, and 20.0±

0.2 degrees measured at reflection angle 2θ

.

2. Crystalline pravastatin sodium of claim 1 wherein the X-ray powder diffraction pattern further comprises peaks at 8.6, 9.2, 10.0, 11.6, 12.0, and 17.0±

0.2 degrees measured at reflection angle 2θ

.

3. Crystalline pravastatin sodium and hydrates thereof of claim 1 further characterized by an infrared spectrum obtained in Nujol Moll comprising absorption bands at 826, 842, 864, 1156, 1184 and 1576±

4 cm<sup>−

1</sup>.

4. Crystalline pravastatin sodium of claim 3 wherein the infrared spectrum further comprises absorption bands at 686, 842, 864, 917, 939, 965, 1013, 1040, 1092, 1111, 1156, 1265, 1310, 1330, and 1726±

2 cm<sup>−

1</sup>.

5. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 1 and a pharmaceutically acceptable carrier.

6. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 5.

7. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 3.6, 6.1 and 6.6 ±

0.2 degrees measured at reflection angle 2θ

.

8. Crystalline pravastatin sodium of claim 7 wherein the X-ray powder diffraction pattern further comprises peaks at 9.0, 9.6, 10.1, 16.4, 16.8 and 18.6±

0.2 degrees measured at reflection angle 2θ

.

9. Crystalline pravastatin sodium and hydrates thereof of claim 7 further characterized by an infrared spectrum obtained in Nujol mull comprising absorption bands at 1149, 1161, 1563 and 1606±

2cm<sup>−

1</sup>.

10. Crystalline pravastatin sodium of claim 9 wherein the infrared spectrum further comprises absorption bands at 614, 692, 739, 824, 842, 854, 868, 901, 914, 936, 965, 1011, 1028, 1039, 1072, 1091, 1111, 1129, 1185, 1232, 1245, 1318, 1711 and 1730±

2 cm<sup>−

1</sup>.

11. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 7 and a pharmaceutically acceptable carrier.

12. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 11.

13. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 13.0, 15.5, 16.0 and 21.0±

0.2 degrees measured at reflection angle 2θ

.

14. Crystalline pravastatin sodium of claim 13 wherein the X-ray powder diffraction pattern further comprises peaks at 4.8, 7.6, 8.7, 10.0, 11.8, 12.4, 17.4, 17.9, 18.4, 19.7, 21.8 and 22.8±

0.2 degrees measured at reflection angle 2θ

.

15. Crystalline pravastatin sodium and hydrates thereof of claim 13 further characterized by an infrared spectrum obtained in Nujol Moll comprising absorption bands at 829, 851, 1078, 1090, 1567, and 1728 ±

2 cm<sup>−

1</sup>.

16. Crystalline pravastatin sodium of claim 15 wherein the infrared spectrum further comprises absorption bands at 742, 870, 926, 940, 964, 1013, 1038, 1146, 1166, 1174, 1194, 1257, 1268, 1313 and 1328±

2 cm<sup>−

1</sup>.

17. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 13 and a pharmaceutically acceptable carrier.

18. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 17.

19. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 6.3 and 9.8±

0.2 degrees measured at reflection angle 2θ

.

20. Crystalline pravastatin sodium of claim 19 wherein the X-ray powder diffraction pattern further comprises peaks at 3.6 and 17.1±

0.2 degrees measured at reflection angle 2θ

.

21. Crystalline pravastatin sodium and hydrates thereof of claim 19 further characterized by an infrared spectrum obtained in Nujol Moll comprising absorption bands at 824, 842, 854, 1157, 1186, 1566, and 1606±

2 cm<sup>−

1</sup>.

22. Crystalline pravastatin sodium of claim 21 wherein the infrared spectrum further comprises absorption bands at 854, 914, 939, 965, 1013, 1041, 1079, 1091, 1266, and 1728±

2 cm<sup>−

1</sup>.

23. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 19 and a pharmaceutically acceptable carrier.

24. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 23.

25. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 4.6, 10.3, 12.1, and 16.6±

0.2 degrees measured at reflection angle 2θ

.

26. Crystalline pravastatin sodium of claim 25 wherein the X-ray powder diffraction pattern further comprises peaks at 9.2, 11.2, 18.3 and 20.6±

0.2 degrees measured at reflection angle 2θ

.

27. Crystalline pravastatin sodium and hydrates thereof of claim 25 further characterized by an infrared spectrum obtained in Nujol Moll comprising absorption bands at 1016, 1043, 1158, 1179, 1573 and 1727±

2 cm<sup>−

1</sup>.

28. Crystalline pravastatin sodium of claim 27 wherein the infrared spectrum further comprises absorption bands at 781, 829, 853, 939, 964, 1078, 1266, 1300, 1329 and 1401±

2 cm<sup>−

1</sup>.

29. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 25 and a pharmaceutically acceptable carrier.

30. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 29.

31. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 3.5, 5.9, 9.0, 10.1 and 17.0±

0.2 degrees measured at reflection angle 2θ

.

32. Crystalline pravastatin sodium of claim 31 wherein the X-ray powder diffraction pattern further comprises peaks at 11.7, 12.1, 14.7, 19.0, 19.9, 20.6, 21.8 and 22.9±

0.2 degrees measured at reflection angle 2θ

.

33. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 31 and a pharmaceutically acceptable carrier.

34. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 33.

35. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 3.5, 5.9, 8.9, 10.1, 17.6, 18.8 and 20.8±

0.2 degrees measured at reflection angle 2θ

.

36. Crystalline pravastatin sodium of claim 35 wherein the X-ray powder diffraction pattern further comprises peaks at 6.8, 11.7, 12.3, 13.3, 14.8, 20.0 and 22.9±

0.2 degrees measured at reflection angle 2θ

.

37. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 35 and a pharmaceutically acceptable carrier.

38. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 37.

39. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 4.4, 5.2, 5.8, 6.5, 13.2, and 14.0±

0.2 degrees measured at reflection angle 2θ

.

40. Crystalline pravastatin sodium of claim 39 wherein the X-ray powder diffraction pattern further comprises peaks at 7.5, 8.3, 9.8, 10.2, 11.2, 16.5, 17.5, 18.3, 18.6, 19.5, 20.5, 21.5 and 23.0±

0.2 degrees measured at reflection angle 2θ

.

41. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 39 and a pharmaceutically acceptable carrier.

42. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 41.

43. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 3.8, 6.0, and 16.3±

0.2 degrees measured at reflection angle 2θ

.

44. Crystalline pravastatin sodium of claim 43 wherein the X-ray powder diffraction pattern further comprises peaks at 3.3, 6.8, 7.5, 8.8, 9.3, 10.2, 11.2, 11.7, 13.5, 13.9, 14.5, 15.6, 17.7, 18.1, 18.7, 19.5, 20.0, 20.3, 21.7, 22.3, 24.2, and 26.1±

0.2 degrees measured at reflection angle 2θ

.

45. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 43 and a pharmaceutically acceptable carrier.

46. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 45.

47. Crystalline pravastatin sodium and hydrates thereof having an X-ray powder diffraction pattern comprising characteristic peaks at 16.6, 17.6, and 18.5±

0.2 degrees measured at reflection angle 2θ

.

48. Crystalline pravastatin sodium of claim 47 wherein the X-ray powder diffraction pattern further comprises peaks at 4.5, 5.0, 9.0, 10.1, 12.3, 13.4, 15.0, 19.5, 20.2, and 22.7±

0.2 degrees measured at reflection angle 2θ

.

49. A pharmaceutical composition comprising the crystalline pravastatin sodium of claim 47 and a pharmaceutically acceptable carrier.

50. A method for treating a patient suffering from atherosclerosis or hypercholesteremia by administering a therapeutically effective amount of the pharmaceutical composition of claim 49.

51. A process for preparing pravastatin sodium Form A comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form A from the solution of pravastatin sodium.

52. The process of claim 51 wherein the protic solvent is a mixture of ethanol and water.

53. The process of claim 51 wherein the aprotic solvent is a polar aprotic solvent.

54. The process of claim 52 wherein the polar aprotic solvent is acetonitrile.

55. The process of claim 51 wherein the aprotic solvent is a non-polar solvent.

56. The process of claim 55 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetrachloride.

57. The process of claim 51 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

58. The process of claim 57 wherein the temperature is about −

10°

C.

59. The process of claim 57 wherein the temperature is about 10°

C.

60. The process of claim 53 wherein the temperature is about 5°

C.

61. The process of claim 51 further comprising cooling the solution of pravastatin sodium.

62. The process of claim 51 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

63. The process of claim 51 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

64. The process of claim 51 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

65. The process of claim 51 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

66. The process of claim 65 wherein the temperature is about 60°

C.

67. A process for preparing pravastatin sodium Form B comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form B from the solution of pravastatin sodium.

68. The process of claim 67 wherein the protic solvent is ethanol.

69. The process of claim 67 wherein the aprotic solvent is a polar aprotic solvent.

70. The process of claim 69 wherein the polar aprotic solvent is acetonitrile.

71. The process of claim 69 wherein the polar aprotic solvent is a mixture of solvents selected from the group consisting of acetonitrile, acetone, and ethyl acetate.

72. The process of claim 67 wherein the aprotic solvent is a non-polar solvent.

73. The process of claim 72 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetrachloride.

74. The process of claim 67 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

75. The process of claim 74 wherein the temperature is about −

10°

C.

76. The process of claim 74 wherein the temperature is about 10°

C.

77. The process of claim 74 wherein the temperature is about 5°

C.

78. The process of claim 67 further comprising cooling the solution of pravastatin sodium.

79. The process of claim 67 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

80. The process of claim 67 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

81. The process of claim 67 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

82. The process of claim 67 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

83. The process of claim 82 wherein the temperature is about 60°

C.

95. The process of claim 75 further comprising cooling the solution of pravastatin sodium.

84. A process for preparing pravastatin sodium Form C comprising the steps of:

(a) dissolving a solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form C from the solution of pravastatin sodium.

85. The process of claim 84 wherein the protic solvent is water.

86. The process of claim 84 wherein the aprotic solvent is a polar aprotic solvent.

87. The process of claim 86 wherein the polar aprotic solvent is a mixture of solvents selected from the group consisting of acetonitrile, acetone, and ethyl acetate.

88. The process of claim 86 wherein the polar aprotic solvent is a mixture of acetonitrile and acetone.

89. The process of claim 84 wherein the aprotic solvent is a non-polar solvent.

90. The process of claim 89 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetra chloride.

91. The process of claim 84 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

92. The process of claim 91 wherein the temperature is about −

10°

C.

93. The process of claim 91 wherein the temperature is about 10°

C.

94. The process of claim 91 wherein the temperature is about 5°

C.

96. The process of claim 84 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

97. The process of claim 84 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

98. The process of claim 84 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

99. The process of claim 84 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

100. The process of claim 99 wherein the temperature is about 60°

C.

101. A process for preparing pravastatin sodium Form D comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form D from the solution of pravastatin sodium.

102. The process of claim 101 wherein the protic solvent is water.

103. The process of claim 101 wherein the aprotic solvent is a polar aprotic solvent.

104. The process of claim 103 wherein the polar aprotic solvent is acetonitrile or acetone.

105. The process of claim 104 wherein the polar aprotic solvent is a mixture of acetonitrile and acetone.

106. The process of claim 101 wherein the aprotic solvent is a non-polar solvent.

107. The process of claim 106 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetrachloride.

108. The process of claim 101 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

109. The process of claim 108 wherein the temperature is about −

10°

C.

110. The process of claim 108 wherein the temperature is about 10°

C.

111. The process of claim 108 wherein the temperature is about 5°

C.

112. The process of claim 101 further comprising cooling the solution of pravastatin sodium.

113. The process of claim 101 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

114. The process of claim 101 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

115. The process of claim 101 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

116. The process of claim 101 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

117. The process of claim 116 wherein the temperature is about 60°

C.

118. A process for preparing pravastatin sodium Form E comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the Form E pravastatin sodium from the solution of pravastatin sodium.

119. The process of claim 118 wherein the protic solvent is a mixture of ethanol and water.

120. The process of claim 118 wherein the aprotic solvent is a polar aprotic solvent.

121. The process of claim 118 wherein the polar aprotic solvent is a mixture of solvents selected from the group consisting of acetonitrile, acetone, and ethyl acetate.

122. The process of claim 118 wherein the aprotic solvent is a non-polar solvent.

123. The process of claim 122 wherein the non-polar solvent is ethyl acetate.

124. The process of claim 123 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetrachloride.

125. The process of claim 118 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

126. The process of claim 125 wherein the temperature is about −

10°

C.

127. The process of claim 125 wherein the temperature is about 10°

C.

128. The process of claim 125 wherein the temperature is about 5°

C.

129. The process of claim 118 further comprising cooling the solution of pravastatin sodium.

130. The process of claim 118 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

131. The process of claim 118 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

132. The process of claim 118 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

133. The process of claim 118 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

134. The process of claim 133 wherein the temperature is about 60°

C.

135. A process for preparing pravastatin sodium Form F comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form F from the solution of pravastatin sodium.

136. The process of claim 135 where the protic solvent is water.

137. The process of claim 135 wherein the aprotic solvent is a polar aprotic solvent.

138. The process of claim 137 wherein the polar aprotic solvent is acetonitrile or acetone.

139. The process of claim 138 wherein the polar aprotic solvent is a mixture of solvents selected from the group consisting of acetonitrile, acetone, and ethyl acetate.

140. The process of claim 135 wherein the aprotic solvent is a non-polar solvent.

141. The process of claim 140 wherein the non-polar solvent is selected from the group consisting hexane, petroleum, ether and carbon tetrachloride.

142. The process of claim 135 wherein crystallizing pravastatin sodium is performed at a temperature of between about −

10°

C. and 10°

C.

143. The process of claim 140 wherein the temperature is about −

10°

C.

144. The process of claim 140 wherein the temperature is about 10°

C.

145. The process of claim 140 wherein the temperature is about 5°

C.

146. The process of claim 135 further comprising cooling the solution of pravastatin sodium.

147. The process of claim 135 further comprising cooling the solution of pravastatin sodium at a rate of about 5.8°

C. per hour to about 35°

C. per hour.

148. The process of claim 135 further comprising cooling the solution of pravastatin sodium at a rate of about 2°

C. per hour.

149. The process of claim 135 wherein pravastatin sodium is at a concentration of about 0.05 to 0.5 M after dilution with the protic solvent.

150. The process of claim 135 further comprising heating the solution of pravastatin sodium to a temperature above 40°

C. prior to the addition of the aprotic solvent.

151. The process of claim 150 wherein the temperature is about 60°

C.

152. A process for preparing pravastatin sodium Form L comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent; and

(c) crystallizing the pravastatin sodium Form L from the solution of pravastatin sodium.

153. The process of claim 152 wherein the protic solvent is water.

154. The process of claim 152 wherein the aprotic solvent is acetone.

155. The process of claim 152 further comprising cooling a solution of pravastatin sodium at a rate of about 2°

C. h<sup>−

1</sup>.

156. A process for preparing pravastatin sodium Form D comprising the steps of:

(a) dissolving any solid form of pravastatin sodium in a protic solvent to form a solution;

(b) diluting the solution of pravastatin sodium with an aprotic solvent;

(c) crystallizing the pravastatin sodium Form L from the solution of pravastatin sodium; and

(d) drying pravastatin sodium Form L to produce Form D.

157. The process of claim 156 wherein drying pravastatin Form L comprises gradual heating to about 60°

C.

158. The process of claim 156 further comprising cooling a solution of pravastatin sodium at a rate of about 2°

C. h<sup>−

1</sup>.

159. Pravastatin sodium Form A.

160. Pravastatin sodium Form B.

161. Pravastatin sodium Form C.

162. Pravastatin sodium Form D.

163. Pravastatin sodium Form E.

164. Pravastatin sodium Form H.

165. Pravastatin sodium Form H1.

166. Pravastatin sodium Form I.

167. Pravastatin sodium Form J.

168. Pravastatin sodium Form L.