Claims
- 1. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 16.6, 16.9, 17.5, 21.3, 21.7 and 22.2±0.2° 2θ.
- 2. The crystalline solid pantoprazole sodium of claim 1 further having peaks in the powder X-ray diffraction pattern at 11.6, 12.2, 13.1, 14.2, 14.8, 20.6, 22.9 and 23.3±0.2° 2θ.
- 3. The crystalline solid pantoprazole sodium of claim 1 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 1.
- 4. The crystalline solid pantoprazole sodium of claim 1 that is a hydrate.
- 5. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium of claim 1.
- 6. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium of claim 1.
- 7. A process for preparing the crystalline solid pantoprazole sodium of claim 1 comprising:
a) providing a solution of pantoprazole, sodium ions and water in acetone, b) precipitating crystals of the pantoprazole sodium of claim 1 from the solution, and c) separating the crystals from the acetone.
- 8. The process of claim 7 wherein the solution is formed by contacting free pantoprazole with acetone and separately contacting a mixture of sodium hydroxide and water with the acetone.
- 9. The process of claim 8 wherein the solution is cooled to 0° C.
- 10. Crystalline solid pantoprazole sodium acetone solvate.
- 11. The crystalline solid pantoprazole sodium acetone solvate of claim 10 containing pantoprazole, sodium cation and acetone in a one to one to one molar ratio.
- 12. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.5, 13.8, 16.5, 17.0, 26.2 and 26.6±0.2 degrees two-theta.
- 13. The crystalline solid pantoprazole sodium of claim 12 further having peaks in the powder X-ray diffraction pattern at 10.1, 10.5, 11.3, 12.0, 13.4, 15.4, 17.6, 18.4, 19.6, 19.9, 23.0, 23.5, 27.9±0.2 degrees two-theta.
- 14. The crystalline solid pantoprazole sodium of claim 12 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 2.
- 15. A process for preparing the pantoprazole sodium of claim 12 comprising:
a) forming a heterogeneous mixture of a condensed pantoprazole sodium selected from the group consisting of pantoprazole sodium Form II and amorphous pantoprazole sodium and acetone, and b) recovering the pantoprazole sodium of claim 12 from the heterogeneous mixture.
- 16. The process of claim 15 wherein the acetone is liquid.
- 17. The process of claim 15 wherein the acetone is vapor.
- 18. Crystalline solid pantoprazole sodium 1-butanol solvate.
- 19. The crystalline solid pantoprazole sodium 1-butanol solvate of claim 18 containing pantoprazole sodium and 1-butanol in a 2 to 1 molar ratio.
- 20. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.8, 12.3, 19.2, 19.7, 20.3 and 20.7±0.2 degrees two-theta.
- 21. The crystalline solid pantoprazole sodium of claim 20 further having peaks in the powder X-ray diffraction pattern at 13.3, 14.0, 16.0, 17.1, 18.6, 22.8, 24.3, 25.3, 25.8±0.2 degrees two-theta.
- 22. The crystalline solid pantoprazole sodium of claim 20 having a powder X-ray diffraction pattern substantially as depicted in FIG. 3.
- 23. A process for preparing the crystalline solid pantoprazole sodium of claim 20 comprising:
a) providing a solution of pantoprazole and sodium ions in 1-butanol, b) crystallizing the pantoprazole sodium of claim 20 from the solution, and c) separating the crystals from the 1-butanol.
- 24. The process of claim 23 wherein the solution is formed by contacting free pantoprazole and 1-butanol and separately contacting solid sodium hydroxide and 1-butanol.
- 25. A process for preparing the pantoprazole sodium 1-butanol solvate of claim 20 comprising:
a) forming a heterogeneous mixture of pantoprazole sodium hydrate and 1-butanol vapor, b) maintaining the mixture for a period of time sufficient to substantially convert all of the pantoprazole sodium hydrate to the pantoprazole sodium of claim 20, and c) separating the pantoprazole sodium of claim 20 from the 1-butanol vapor.
- 26. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 17.9, 19.5, 20.4, 21.4, 24.6±0.2 degrees two-theta.
- 27. The crystalline solid pantoprazole sodium of claim 26 further having peaks in powder X-ray diffraction pattern at 6.3, 10.1, 15.5, 20.7, 23.0, 26.3, 29.4 and 29.9±0.2 degrees two-theta.
- 28. The crystalline solid pantoprazole sodium of claim 26 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 4.
- 29. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium of claim 26.
- 30. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium of claim 26.
- 31. A crystalline solid pantoprazole sodium hydrate having a water content of from about 10 to about 30 percent by weight.
- 32. A process for preparing the crystalline solid pantoprazole sodium of claim 26 comprising:
a) forming a solution of pantoprazole sodium in a mixture of methanol and water, b) crystallizing pantoprazole sodium of claim 26 from the solution, and c) separating the crystals from the mixture of methanol and water.
- 33. A process for preparing the crystalline solid pantoprazole sodium of claim 26 comprising:
a) forming a heterogenous mixture of pantoprazole sodium Form II and water vapor, and b) maintaining the heterogeneous mixture for a period of time sufficient to effect the conversion Form II to the crystalline solid pantoprazole sodium of claim 26.
- 34. Crystalline solid pantoprazole sodium methylethylketone solvate.
- 35. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.6, 12.1, 13.0, 13.7±0.2 degrees two-theta.
- 36. The crystalline solid pantoprazole sodium of claim 35 further having peaks in the powder X-ray diffraction pattern at 15.8, 16.1, 16.8, 17.1, 19.4, 20.0, 20.5, 22.6, 24.1, 24.5, 25.2, 25.5, 27.2±0.2 degrees two-theta.
- 37. The crystalline solid pantoprazole sodium of claim 35 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 5.
- 38. A process for preparing the pantoprazole sodium of claim 35 comprising:
a) forming a heterogeneous mixture of pantoprazole sodium and methylethylketone, b) maintaining the heterogeneous mixture for a period of time sufficient to convert substantially all of the pantoprazole sodium into the pantoprazole sodium of claim 35, and c) separating the pantoprazole sodium of claim 35 from the methylethylketone.
- 39. The process of claim 38 wherein the pantoprazole sodium in step (a) is pantoprazole sodium Form II.
- 40. Crystalline solid pantoprazole sodium dimethylcarbonate solvate.
- 41. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.3, 13.6, 16.9, 17.3±0.2 degrees two-theta.
- 42. The crystalline solid pantoprazole sodium of claim 41 further having peaks in the powder X-ray diffraction pattern at 10.6, 11.2, 18.5, 19.3, 19.9, 21.2, 22.8, 26.1, 26.7±0.2 degrees two-theta.
- 43. The crystalline solid pantoprazole sodium of claim 42 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 6.
- 44. A process for preparing the pantoprazole sodium of claim 41 comprising:
a) forming a heterogeneous mixture of pantoprazole sodium and dimethylcarbonate, b) maintaining the heterogeneous mixture for a period of time sufficient to convert substantially all of the pantoprazole sodium into the pantoprazole sodium of claim 41, and c) separating the pantoprazole sodium of claim 41 from the dimethylcarbonate.
- 45. Crystalline solid pantoprazole sodium 1-propanol solvate.
- 46. The crystalline solid pantoprazole sodium 1-propanol solvate of claim 45 containing pantoprazole sodium and 1-propanol in a one to one molar ratio.
- 47. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 16.4, 18.3, 19.0, 19.7, 21.9±0.2 degrees two-theta.
- 48. The crystalline solid pantoprazole sodium of claim 47 further having peaks in the powder X-ray diffraction pattern at 10.9, 11.3, 13.6, 14.2, 15.5, 23.2, 24.7, 25.6, 25.8, 28.2±0.2 degrees two-theta.
- 49. The crystalline solid pantoprazole sodium of claim 47 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 7.
- 50. A process for preparing the pantoprazole sodium of claim 47 comprising:
a) forming a solution of pantoprazole and sodium ions in 1-propanol, b) crystallizing the pantoprazole sodium claim 47 from the solution, and c) separating the crystals from the 1-propanol.
- 51. The process of claim 50 wherein the solution is formed by contacting free pantoprazole and 1-propanol and separately contacting solid sodium hydroxide and 1-propanol.
- 52. Crystalline solid pantoprazole sodium anhydrate.
- 53. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 6.0, 16.0, 24.4, 25.1, 25.8±0.2 degrees two-theta.
- 54. The crystalline solid pantoprazole sodium of claim 53 further having peaks in the powder X-ray diffraction pattern at 14.9, 16.7, 17.0, 18.2, 20.5, 21.6, 23.2±0.2 degrees two-theta.
- 55. The crystalline solid pantoprazole sodium of claim 54 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 8.
- 56. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium of claim 53.
- 57. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium of claim 53.
- 58. A process for preparing the pantoprazole sodium of claim 53 comprising:
a) forming a solution by contacting a pantoprazole sodium hydrate with methanol, b) drying the solution, c) evaporating methanol from the dried solution leaving a non-crystalline residue, d) forming a heterogeneous mixture of the residue and acetone, e) maintaining the heterogeneous mixture for a period of time sufficient to convert substantially all of the residue into crystals, and f) separating the crystals from the acetone.
- 59. Crystalline solid pantoprazole sodium 2-methylpropanol solvate.
- 60. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.6, 15.7, 19.4, 24.7, 28.3±0.2 degrees two-theta.
- 61. The crystalline solid pantoprazole sodium of claim 60 further having peaks in the powder X-ray diffraction pattern at 11.1, 13.6, 16.0, 18.4, 19.4, 20.9, 22.2, 23.0, 25.3, 25.8±0.2 degrees two-theta.
- 62. The crystalline solid pantoprazole sodium of claim 61 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 9.
- 63. A process of preparing the pantoprazole sodium of claim 60 comprising the steps of:
a) forming a solution of pantoprazole sodium in 2-methylpropanol, b) crystallizing the pantoprazole sodium of claim 60 from the solution, and c) separating 2-methylpropanol from the crystals.
- 64. The process of claim 63 wherein the solution is heated to reflux temperature.
- 65. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 6.7, 15.9, 23.6, 27.7, 29.3, 30.6±0.2 degrees two-theta.
- 66. The crystalline solid pantoprazole sodium of claim 65 further having peaks in the powder X-ray diffraction pattern at 13.4, 13.9, 17.1, 19.2, 20.4, 21.0, 25.9±0.2 degrees two-theta.
- 67. The crystalline solid pantoprazole sodium of claim 66 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 10.
- 68. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium of claim 65.
- 69. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium of claim 65.
- 70. Pantoprazole sodium hydrate having a water content of from about 7 to about 10 percent by weight.
- 71. A process for preparing the crystalline solid pantoprazole sodium of claim 65 comprising:
a) forming a solution of pantoprazole sodium in a diluent selected from the group consisting of lower ketones and 2-propanol, b) crystallizing pantoprazole sodium from the solution, and c) separating the crystals from the diluent.
- 72. The process of claim 71 wherein the lower ketones are methyl ethyl ketone and acetone.
- 73. The process of claim 71 wherein the solution is heated to reflux temperature.
- 74. A solid state thermal conversion process for preparing the crystalline solid pantoprazole sodium of claim 65 comprising heating a solvate of pantoprazole sodium selected from the group consisting of pantoprazole sodium 1-butanol solvates and pantoprazole sodium 2-methylpropanol solvates.
- 75. The process of claim 74 wherein the solvate is heated to from about 50° C. to about 80° C.
- 76. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 5.7, 17.0, 18.1, 22.7 and 25.8±0.2 degrees two-theta.
- 77. The crystalline solid pantoprazole sodium of claim 76 further having peaks in the powder X-ray diffraction pattern at 10.2, 10.9, 13.3, 14.1 and 27.6±0.2 degrees two-theta.
- 78. The crystalline solid pantoprazole sodium of claim 77 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 11.
- 79. A process for preparing the crystalline solid pantoprazole sodium of claim 76 comprising:
a) forming a heterogeneous mixture of crystalline pantoprazole sodium and 1-propanol vapor, b) maintaining the mixture for a period of time sufficient to substantially convert the crystalline pantoprazole sodium to Form XIV, and c) separating the 1-propanol vapors from Form XIV.
- 80. A process for preparing the crystalline solid pantoprazole sodium of claim 76 comprising:
a) forming a homogeneous mixture of pantoprazole sodium and liquid 1-propanol, b) adding at least one crystal of pantoprazole sodium hydrate Form XIV to the homogeneous mixture, c) precipitating pantoprazole sodium as Form XIV from the homogeneous mixture, and d) separating the 1-propanol from Form XIV.
- 81. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern having peaks at 20.7, 21.4, 21.8 and 23.3±0.2 degrees two-theta.
- 82. The crystalline solid pantoprazole sodium of claim 81 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 12.
- 83. The crystalline solid pantoprazole sodium of claim 81 further having peaks in the powder X-ray diffraction pattern at 5.3, 11.6, 14.1, 14.8, 16.0 and 19.0±0.2 degrees two-theta.
- 84. The crystalline solid pantoprazole sodium of claim 83 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 12.
- 85. A process for preparing the crystalline solid pantoprazole sodium of claim 81 comprising:
a) providing crystals of pantoprazole sodium Form XIV, and b) heating the Form XIV crystals for a period of time sufficient to convert substantially all of the crystals to the crystalline solid pantoprazole sodium of claim 81.
- 86. Crystalline solid pantoprazole sodium hydrate characterized by a powder X-ray diffraction pattern having peaks at 10.8, 11.4, 12.1 and 22.4±0.2 degrees two-theta.
- 87. The crystalline solid pantoprazole sodium of claim 86 further having peaks in the powder X-ray diffraction pattern at 5.5, 17.4, 24.3, 24.8±0.2 degrees two-theta.
- 88. The crystalline solid pantoprazole sodium of claim 87 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 13.
- 89. A process for preparing the crystalline solid pantoprazole sodium of claim 86 comprising:
a) forming a homogeneous mixture of sodium pantoprazole and toluene, b) precipitating the pantoprazole sodium of claim 86 from the mixture, and c) separating the toluene from pantoprazole sodium of claim 86.
- 90. The process of claim 89 wherein the homogeneous mixture is formed by contacting free pantoprazole with the toluene and separately contacting a source of sodium ions with the toluene.
- 91. Crystalline solid pantoprazole sodium hydrate-methylethylketone solvate.
- 92. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern generated using CuKα radiation with peaks at 15.2, 15.7, 25.8, and 26.5±0.2 degrees two-theta.
- 93. The crystalline solid pantoprazole sodium of claim 92 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 14.
- 94. A process for preparing the crystalline solid pantoprazole sodium of claim 92 comprising:
a) agitating a heterogeneous mixture of pantoprazole sodium in a diluent selected from the group consisting of methyl ethyl ketone and a mixture of methyl ethyl ketone with either added water or adventitious water under conditions effective for converting the pantoprazole sodium to the pantoprazole sodium of claim 92, and b) separating the diluent from the pantoprazole sodium of claim 92.
- 95. The process of claim 94 wherein the heterogeneous mixture is agitated by stirring with a stirrer revolving at a rate of 700 revolutions per minute or more.
- 96. Crystalline solid pantoprazole sodium hydrate-acetone solvate.
- 97. Crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern generated using CuKα radiation with peaks at 11.2, 13.2, 13.5, 13.8, 14.1±0.2 degrees two-theta.
- 98. The crystalline solid pantoprazole sodium of claim 97 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 15.
- 99. A process for preparing the crystalline solid pantoprazole sodium of claim 97 comprising:
a) forming a heterogeneous mixture of pantoprazole sodium with a diluent selected from the group consisting of acetone and mixtures of acetone and either added water or adventitious water, b) maintaining the mixture under conditions to effect the conversions to the pantoprazole sodium of claim 97, and c) separating the diluent from the pantoprazole sodium of claim 97.
- 100. Crystalline solid pantoprazole sodium dihydrate.
- 101. The crystalline solid pantoprazole sodium characterized by a powder X-ray diffraction pattern generated using CuKα radiation with peaks at 11.3, 13.4, 13.8, 26.2 and 26.6±0.2 degrees two-theta.
- 102. The crystalline solid pantoprazole sodium of claim 101 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 16.
- 103. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium dihydrate of claim 101.
- 104. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium dihydrate of claim 101.
- 105. A process for preparing the pantoprazole sodium dihydrate of claim 100 comprising
a) forming a heterogeneous mixture of pantoprazole sodium and water, b) evaporating the water, and c) optionally, drying the residue left after evaporation.
- 106. Crystalline solid pantoprazole sodium trihydrate.
- 107. The crystalline solid pantoprazole sodium of claim 106 characterized by a powder X-ray diffraction pattern generated using CuKα radiation with peaks at 15.4, 17.9, 24.6, 25.9, 26.2, and 26.5±0.2 degrees two-theta.
- 108. The crystalline solid pantoprazole sodium of claim 107 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 17.
- 109. A pharmaceutical composition comprising the crystalline solid pantoprazole sodium trihydrate of claim 107.
- 110. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium trihydrate of claim 107.
- 111. A process for preparing the pantoprazole sodium of claim 107 comprising:
a) forming a heterogeneous mixture of pantoprazole sodium and a liquid phase of 1 to 10 weight percent water and 99 to 90 weight percent liquid hydrocarbon, b) maintaining the heterogenous mixture under conditions effective for converting the pantoprazole sodium to the pantoprazole sodium of claim 107, c) separating the liquid phase from the pantoprazole sodium of claim 107, and d) optionally, drying the pantoprazole sodium of claim 107.
- 112. The process of claim 111 wherein the liquid hydrocarbon is an aromatic or an aliphatic hydrocarbon.
- 113. The process of claim 112 wherein the liquid hydrocarbon is benzene having one or more substituents that collectively contain from one to six carbon atoms.
- 114. The process of claim 112 wherein the liquid hydrocarbon is an aliphatic hydrocarbon having from five to twelve carbon atoms.
- 115. The process of claim 111 wherein the liquid phase contains from about 1 to about 5 weight percent water.
- 116. Amorphous pantoprazole sodium.
- 117. The crystalline solid pantoprazole sodium of claim 116 having a Powder X-ray diffraction pattern substantially as depicted in FIG. 18.
- 118. A pharmaceutical composition comprising the amorphous pantoprazole sodium of claim 116.
- 119. A method of treating gastroesophageal reflux disease comprising administering to a patient afflicted with the disease the crystalline solid pantoprazole sodium trihydrate of claim 116.
- 120. A process for preparing the amorphous pantoprazole sodium of claim 116 comprising heating crystals of a pantoprazole sodium solvate with a solvent selected from the group consisting of water, 1-butanol and 2-methylpropanol for a period of time sufficient to disrupt the crystal lattice of substantially all of the crystals.
- 121. A process for preparing the amorphous pantoprazole sodium of claim 116 comprising
a) forming a solution of pantoprazole sodium in a C1-C4 alcohol, b) evaporating the alcohol to leave a semi-solid or liquid residue, c) forming a heterogeneous mixture of the residue and a liquid in which pantoprazole sodium is not appreciably soluble, d) maintaining the mixture until the residue solidifies into amorphous pantoprazole sodium, and e) separating the amorphous pantoprazole sodium from the liquid.
- 122. A process for preparing the amorphous pantoprazole sodium of claim 116 comprising:
a) forming a solution of pantoprazole sodium in acetonitrile, b) precipitating amorphous pantoprazole sodium from the solution, and c) separating the amorphous pantoprazole from the acetonitrile.
- 123. The process of claim 122 wherein precipitation is induced by adding a liquid in which pantoprazole is not appreciably soluble to the solution.
- 124. A process for preparing the amorphous pantoprazole sodium of claim 116 comprising:
a) providing crystals of pantoprazole sodium, b) heating the crystalline pantoprazole sodium to an elevated temperature, and c) maintaining the elevated temperature for a period of time sufficient to disrupt the crystal lattice of substantially all of the crystals.
- 125. The process of claim 124 wherein the pantoprazole sodium in step a is pantoprazole sodium sesquihydrate.
- 126. A process for preparing the amorphous pantoprazole sodium of claim 116 comprising:
a) forming a solution of pantoprazole sodium in toluene, b) precipitating amorphous pantoprazole sodium from the solution, and c) separating the amorphous pantoprazole sodium from the toluene.
- 127. The process of claim 126 wherein the solution is formed by contacting free pantoprazole with the toluene and separately contacting a source of sodium ions with the toluene.
- 128. The process of claim 124 wherein the elevated temperature is at least 100° C.
- 129. A process for preparing pantoprazole sodium monohydrate comprising:
a) forming a solution of pantoprazole and sodium hydroxide in a diluent selected from the group consisting of tetrahydrofuran, methanol, 2-propanol, butanol, dimethylcarbonate, acetone, acetonitrile and 1-propanol, b) precipitating crystals of pantoprazole sodium monohydrate from the solution, and c) separating the crystals from the diluent.
- 130. The process of claim 129 wherein the diluent is 2-propanol and the solution is formed by contacting free pantoprazole with the diluent and separately contacting sodium hydroxide with the diluent.
- 131. The process of claim 129 wherein the solution is formed by contacting pantoprazole sodium monohydrate with the diluent.
- 132. A process for preparing pantoprazole sodium monohydrate comprising:
a) forming a heterogeneous mixture by contacting pantoprazole sodium and a diluent selected from the group consisting of dimethylcarbonate and acetone, and b) recovering pantoprazole sodium monohydrate Form I from the heterogeneous mixture.
- 133. The process of claim 132 wherein the pantoprazole sodium that is contacted with the diluent is selected from the group of solid state forms of pantoprazole sodium consisting of pantoprazole sodium Form II, amorphous pantoprazole sodium and pantoprazole sodium sesquihydrate.
- 134. A process for preparing pantoprazole sodium sesquihydrate comprising the steps of:
a) forming a solution of pantoprazole and sodium hydroxide in a diluent selected from the group consisting of 2-propanol, tetrahydrofuran, acetonitrile, methanol, ethanol, water, mixtures of sec-butanol and dichloromethane, and ethyl acetate, b) precipitating crystals of pantoprazole sodium sesquihydrate from the solution, and c) separating the crystals from the diluent.
- 135. The process of claim 134 wherein the diluent is selected from the group consisting of methanol and ethanol and the solution is formed by contacting free pantoprazole with the diluent and separately contacting a source of sodium ions with the diluent.
- 136. The process of claim 135 wherein the source of sodium ions is a mixture of sodium hydroxide and water.
- 137. The process of claim 136 wherein the pantoprazole sodium monohydrate is pantoprazole sodium monohydrate Form II.
- 138. A process for preparing pantoprazole sodium sesquihydrate comprising the steps of:
a) forming a heterogeneous mixture by contacting pantoprazole sodium and a diluent selected from the group consisting of ethyl acetate, dichloromethane, water, dimethylcarbonate and 2-propanol, and b) recovering pantoprazole sodium sesquihydrate from the heterogeneous mixture.
- 139. The process of claim 138 wherein the diluent is selected from the group consisting of water and mixtures of water and 2-propanol, and the diluent is added in a minor amount relative to the pantoprazole sodium on a weight basis.
- 140. The process of claim 138 wherein the diluent is selected from the group consisting of ethyl acetate, dichloromethane, water and dimethylcarbonate and the diluent is added in an amount equal to or greater than the amount of pantoprazole sodium on a weight basis.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/434,445, filed on Dec. 19, 2002 and U.S. Provisional Patent Application Serial No. 60/453,836, filed Mar. 12, 2003, the disclosures of which are hereby incorporated by reference in their entirety.
Provisional Applications (2)
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Number |
Date |
Country |
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60434445 |
Dec 2002 |
US |
|
60453836 |
Mar 2003 |
US |