Multiple approaches to pharmaceutical polymorphism investigation--a case study.
Polymorph screening of Compound A, an investigational drug, revealed two anhydrous polymorphs (Forms I and II) and two monohydrates (Forms III and IV) of this pharmaceutical solid. The physiochemical properties of the four forms were characterized by thermal analysis, hot-stage microscopy, equilibrium solubility and intrinsic dissolution rate measurements, and X-ray powder diffraction. Inter-conversion relationship of the four forms was fully elucidated. Thermodynamic stability relationship was inferred from melting data for Form I and Form II and evaluated by van't Hoff plot for Form III and Form IV. Form I and Form III were found to be the more stable anhydrous and hydrate form, respectively. Anhydrous Form I was selected for further pharmaceutical development.
Li
Haitao
H
Small Molecule Process and Product Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Kiang
Y-H
YH
Jona
Janan
J
D000085:Acetates / Q000032:analysis / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization / Q000379:methods; D005663:Furans / Q000032:analysis / Q000737:chemistry; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D011208:Powders; D013816:Thermodynamics; D014961:X-Ray Diffraction / Q000379:methods
D000085:Acetates; D005663:Furans; D004364:Pharmaceutical Preparations; D011208:Powders; C018674:tetrahydrofuran; C007650:ethyl acetate