Thermodynamic stability relationship of polymorphs and hydrates of an investigational drug

I&EC 42

Haitao Li, Y-H. Kiang, Janan Jona, and Drazen Ostovic. Department of Pharmaceutics, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320
Polymorph screening of AMG-XXX, an investigational drug, revealed two anhydrous polymorphs (Forms I and II) and two monohydrates (Forms III and IV) of this pharmaceutical solid. The aim of this study was to compare the thermodynamic stability of the four forms. 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. In addition, intrinsic dissolution rates of the four forms were measured in 50 mM phosphate buffer with 0.5%(v/w) SDS at pH 7 and 37ºC and correlated well with their thermodynamic stability.
 

Poster Session
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Industrial & Engineering Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006