Crystalline Forms Of [R-(R*,R*)-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methyl- Ethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic Acid Calcium Salt (2:1)

Abstract

Novel crystalline forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt designated Form V, Form VI, Form VII, Form VIII, Form IX, Form X, Form XI, Form XII, Form XIII, Form XIV, Form XV, Form XVI, Form XVII, Form XVIII, and Form XIX are characterized by their X-ray powder diffraction, solid-state NMR, and/or Raman spectroscopy are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, and Alzheimer's disease.

1 . A solid pharmaceutical composition comprising crystalline Form X atorvastatin or a hydrate thereof having an X-ray powder diffraction containing the following 2θ values measured using CuK α  radiation: 4.7, 5.2, 5.8, 6.9, 7.9, 9.2, 9.5, 10.3 (broad), 11.8, 16.1, 16.9, 19.1, 19.8, 21.4, 22.3 (broad), 23.7 (broad), 24.4, and 28.7, and at least one pharmaceutically acceptable excipient, diluent or carrier. 
   
   
       2 . A solid pharmaceutical composition comprising crystalline Form X atorvastatin or a hydrate thereof characterized by solid state  13 C nuclear magnetic resonance having the following chemical shifts expressed in parts per million: 18.3, 20.3, 25.3, 26.4, 40.9, 43.7, 71.1, 119.9, 123.2, 127.9, 129.4, 134.8, 137.9, 159.4, 165.5, 179.5, and 187.0, and at least one pharmaceutically acceptable excipient, diluent or carrier. 
   
   
       3 . A solid pharmaceutical composition comprising crystalline Form X atorvastatin or a hydrate thereof characterized by Raman spectroscopy having the following peaks expressed in cm −1 : 116, 824, 999, 1034, 1158, 1240, 1369, 1411, 1478, 1525, 1603, 1650, 2911, and 3062, and at least one pharmaceutically acceptable excipient, diluent or carrier.