| 摘要 |
1. Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-'beta','delta'-dihydroxy-5-(1-methylphenyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid (atorvastatin) and hydrates thereof characterized in that of crystalline form I atorvastatin having the characteristics given in Tables 1 and 2: TABLE 1. Intensities and Peak Locations of all Diffraction Lines With Relative Intensity Greater Than 20% for Form I Atorvastatin 29 d Relative Intensity (>20%) NoGrinding Relative Intensity (>20%)* Ground 2 Minutes 9.150 9.6565 37.42 42.60 9.470 9.3311 46.81 41.94 10.266 8.6098 75.61 55.67 10.560 8.3705 24.03 29.33 11.853 7.4601 55.16 41.74 12.195 7.2518 20.03 24.62 17.075 5.1887 25.95 60.12 19.485 4.5520 89.93 73.59 21.626 4.1059 100.00 100.00 21.960 4.0442 58.64 49.44 22.748 3.9059 36.95 45.85 23.335 3.8088 31.76 44.72 23.734 : 3.7457 87.55 63.04 24.438 3.6394 23.14 21.10 28.915 3.0853 21.59 23.42 29.234 3.0524 20.45 23.36 * The second relative intensity column gives the relative intensities of the diffraction lines on the original diffractogram after 2 minutes of grinding. TABLE 2. Carbon Atom Assignment and Chemical Shift for Form I Atorvastatin Assignment (7 kHz) Chemical Shift C12 or C25 182.8 C12 or C25 178.4 C16 166.7 (broad) and 159.3 Aromatic Carbons C2-C5, C13-C18, C19-C24, C27-C32 137.0 134.9 131.1 129.5 127.6 123.5 120.9 118.2 113.8 C8,C10 73.1 70.5 68.1 64.9 Methylene Carbons C6, C7, C9, Cll 47.4 41.9 40.2 C33 26.4 25.2 C34 21.3 dissolving crystalline form I atorvaststin in a non-hydroxylic solvent and subsequent removing the solvent. 2. A process according to Claim 1 wherein the non-hydroxyiic solvent in Step (a) is selected from the group consisting of: tetrahydrofuran, and mixtures of tetrahydrofuran and toluene. 3. A process according to Claim 2 wherein the solvent is a mixture of tetrahydrofuran and toluene. 4. A process according to Claim 1 wherein the solvent is removed by vacuum drying or spray drying. 5. A process according to Claim 4 wherein the solvent is removed by vacuum drying. 6. A process according to Claim 5 wherein vacuum drying is initially carried out at about 20 degree C to about 40 degree C and subsequently at about 70 degree C to about 90 degree C under vacuum at about 5 mm Hg to about 25 mm Hg. 7. A process according to Claim 6 wherein vacuum drying is initially carried out at about 35 degree C and subsequently at about 85 degree C under vacuum at about 5 mm Hg to about 25 mm Hg. 8. A process according to Claim 5 wherein the material obtained after drying is a brittle foam which is broken up by mechanical agitation. |
