Patent EA-000474-B1 (EA)
Title: Crystalline [r-(r*, r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin)
Inventor: BRIGGS CHRISTOPHER A
IPC: C07D/
Filed: 1996-07-08
Abstract: 1. A crystalline Form I atorvastatin or a hydrate thereof having an X-ray powder diffraction containing as a parent peak the following 2θ value measured using CuKα radiation: 21.6. 2. A crystalline Form 1 atorvastatin or a hydrate thereof according to Claim 1 further containing the following 2θ values measured using CuKα radiation: 17.1, 19.5 and 23.7. 3. A crystalline Form I atorvastatin or a hydrate thereof according to Claim 2 further containing the following 2θ values measured using CuKα radiation: 9.2, 9.5, 10.3, 11.9, 22.0, 22.7 and 23.3. 4. A crystalline Form I atorvastatin or a hydrate thereof having an X-ray powder diffraction containing the following 2θ values measured using CuKα radiation 9.2, 9.5, 10.3, 10.6, 11.9, 12.2, 17.1, 19.5, 21.6, 22.0, 22.7, 23.3, 23.7, 24.4, 28.9 and 29.2. 5. A crystalline Form I atorvastatin or a hydrate thereof having an X-ray powder diffraction containing at least one of the following 2θ values measured using CuKα radiation: 11.9 or 22.0. 6. A crystalline Form I atorvastatin or a hydrate thereof characterized by solid-state C<13> nuclear magnetic resonance having the following chemical shifts expressed in parts per million: 21.3, 25.2, 26.4, 40.2, 41.9, 47.4, 64.9, 68.1, 70.5, 73.1, 113.8, 118.2, 120.9, 123.5, 127.6, 129.5, 131.1, 134.9, 137.0, 159.3, 166.7 (broad), 178.4 and 182.8. 7. The crystalline Form I atorvastatin according to any one of the preceding Claims containing 1 to 8 moles of water. 8. The crystalline Form I atorvastatin according to any one of the preceding Claims containing 3 moles of water. 9. Crystalline Form II atorvastatin or a hydrate thereof having an X-ray powder diffraction containing as a parent peak the following 2θ value measured using CuKα radiation: 8.5. 10. Crystalline Form II atorvastatin or a hydrate thereof according to Claim 9 further containing the following 2θ values measured using CuKα radiation: 9.0 and 20.5. 11. Crystalline Form II atorvastatin or a hydrate thereof according to Claim 10 further containing the following 2θ values measured using CuKα radiation: 5.6, 17.1 - 17.4 (broad), 19.5 and 22.7 - 23.2 (broad). 12. Crystalline Form II atorvastatin or a hydrate thereof having an X-ray powder diffraction containing the following 2θ values measured using CuKα radiations 5.6, 7.4, 8.5, 9.0, 12.4 (broad), 15.8 (broad), 17.1 - 17.4 (broad), 19.5, 20.5, 22.7-23.2 (broad), 25.7 (broad) and 29.5. 13. Crystalline Form IX atcorvastabin or a hydrate thereof containing the following 2θ values measured using CuKα radiation: 9.0 and 20.5. 14. Crystalline Form II atorvastatin or a hydrate thereof characterized by solid-state C<13> nuclear magnetic resonance having the following chemical shifts expressed in parts per million: 22.8 (broad), 27.5, 40.2, 41.7, 42.3, 43.4, 67.3, 68.0, 69.0, 70.6, 114.7, 115.7, 117.1, 119.0, 120.3, 121.4, 122.9, 129.0, 133.3, 134.8, 140.5, 161 (broad), 163 (broad) and 181 (broad). 15. Crystalline Form IV atorvastatin or a hydrate thereof having an X-ray powder diffraction containing as a parent peak the following 2θ value measured using CuKα radiation: 8.0. 16. Crystalline Form IV atorvastatin or a hydrate thereof according to Claim l5 further containing the following 2θ value measured using CuKα radiation: 9.7. 17. Crystalline Form IV atorvastatin or a hydrate thereof according to Claim 16 further containing the following 2θ value measured using CuKα radiation; 19.6. 18. Crystalline Form IV atorvastatin or a hydrate thereof having an X-ray powder diffraction containing the following 2θ values measured using CuKα radiation: 4.9, 5.4, 5.9, 8.0, 9.7, 10.4, 12.4, 17.7, 18.4, 19.2, 19.6, 21.7, 23.0, 23.7 and 24.1. 19. Crystalline Form IV atorvastatin or a hydrate thereof having an X-ray powder diffraction containing at least one of the following 2θ value measured using CuKα radiation: 8.0 or 9.7. 20. Crystalline Forrn IV atorvastatin or a hydrate thereof characterized by solid-state <13>C nuclear magnetic resonance having the following chemical shifts expressed in parts per million: 17.9, 19.4, 20.3, 25.9, 40.0, 42.1, 43-4, 46.1, 63.5, 66.3, 67.9, 71.5, 115.7, 119.8, 122.7, 127.1, 129.2, 134.7, 138.1 (broad), 159.0 (broad), 166.1 (broad), 179.3, 181.4, 184.9 and 1S6.4. 21. A pharmaceutical composition comprising crystalline Form I, Form II or Form IV atorvastatin or a hydrate thereof according to any one of the preceding Claims in admixture with at least one pharmaceutically acceptable excipient, diluent or carrier. 22. A pharmaceutical composition according to Claim 21 in the form of tablets, pills, dispersible granules, cachete, capsules, powders, lozenges, suppositories or retentxon enemas.