ANYL 204 |
| Many factors may affect solvent-mediated polymorphic transformation. High solubility reduces the energy barrier of the nucleation of the most stable polymorph, and hastens the transformation. However, certain strong solvent-solute interactions may inhibit the nucleation of the most stable polymorph. The impurities that are structurally related to the drug compound may selectively stabilize the metastable polymorph. Solvent-mediated polymorphic transformation was found to be hastened by reducing the particle size, increasing the specific surface area, and/or introducing crystal defects and amorphous content into the metastable sample. Excess of the metastable solid also frequently affects the conversion of the metastable polymorph to its corresponding most stable polymorph. The knowledge on the factors that affect solvent-mediated polymorphic transformation can provide a guideline in optimizing the experimental procedure of finding the thermodynamically most stable polymorph at the earliest stage of exploratory development in pharmaceutical industry. |
|
Characterization of Polymorphic Compounds and Mixtures
1:30 PM-4:55 PM, Monday, 11 September 2006 Moscone Center -- Room 130, Oral
Division of Analytical Chemistry |