A Molecular Simulation Approach to Control the Crystallization of Pharmaceutical Compounds During Dissolution

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CTS - 9526328 Nair Rodriquez-Hornedo University of Michigan ABSTRACT The project aims at understanding the molecular processes that control crystallization during dissolution of metastable solid phases in the presence of surfactants. The objectives include identifying the role of metastable solid phases on the nucleation of stable molecular crystals and explaining the effects of surfactant association on nucleation mechanism and crystal morphology. Experiments will be performed using dihydrate carbamazepine as a model drug and two types of surfactant, aliphatic long-chain surfactants and bile salts. Molecular modeling will be used to study the role of crystallographic parameters and molecular structure of dominant crystal faces. The key question is whether nucleation of the stable crystalline phase is enhanced by crystal surfaces of the dissolving metastable phase. If nucleation occurs at very low supersaturations, the drug concentration in solution may never reach the desired levels. The results on the effects of surfactants on nucleation and crystallization will be particularly useful to the pharmaceutical industry and may also have an impact on the manufacturing of specialty chemicals.