IEC 55 |
| Ron C. Kelly and Naír Rodríguez-Hornedo. Pharmaceutical Sciences, University of Michigan, 428 Church Street, College of Pharmacy, Ann Arbor, MI 48109 |
| Intermolecular interactions between additive and drug molecules affecting nucleation and morphology are essential for understanding mechanisms of selective polymorph crystallization. This research investigated the effects of additives on carbamazepine (CBZ) nucleation in aqueous and organic solutions. Carbamazepine exists as three anhydrous (monoclinic, trigonal, triclinic) polymorphs, a dihydrate, and a monoacetonate. Rate-limiting steps for phase transformations and intermolecular interactions directing crystallization were identified. In aqueous solutions, additives with hydrogen bond acceptor:donor ratio ³ 1 decreased CBZ dihydrate {111} growth and delayed the anhydrous to dihydrate phase transformation. In organic solutions, CBZ trigonal preferentially crystallized in solvents accepting or donating hydrogen bonds, while monoclinic and trigonal concomitantly crystallized in solvents that accept/donate or have no hydrogen bond potential. Molecular simulations indicated that specific interactions between additives and CBZ crystal faces lead to inhibition of molecular assemblies necessary for nucleation. These results have significant implications for facilitating or retarding nucleation of metastable polymorphs. |
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Industrial Crystallization (sponsored by Separation Science & Technology Subdivision)
8:30 AM-12:10 PM, Monday, March 24, 2003 Convention Center -- Room 393, Oral
Division of Industrial and Engineering Chemistry |