Arunprakash T. Karunanithi, U.S. Environmental Protection Agency, 26 W. Martin Luther King Drive, Cincinnati, OH 45268, Charles Acquah, Chemical Engineering, University of Connecticut, Storrs, CT 06269, Luke E. K. Achenie, Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Randolph Hall 133, Blacksburg, VA 24061, Shanthakumar Sithambaram, Department of Chemistry, University of Connecticut, Storrs, CT 06269, and Steven Suib, Department of Chemistry, Chemical Engineering and Institute of Material Science, University of Connecticut, Storrs, CT 06269.
This study presents a combined Experimental, Computer-Aided Molecular Design (CAMD) and Database Search approach for designing solvent for pharmaceutical processes. The effect of different solvents on the morphology of pharmaceutical compounds were assessed through experiments. Experimental results reveal that, the hydrogen bonding solubility parameter, solvent viscosity and the structural similarity between solute and solvent were the key properties influencing crystal morphology. These properties were incorporated in the CAMD solvent design framework in the form of morphological constraints. Similarly in the Database Search approach, solvents were selected by matching solvents present in a database with the key properties of solvents having specific values.
Validation of crystal morphology for both the CAMD approach and Solvent Database Search method yielded consistent results. With the aid of the integrated approach, a complete step-by-step procedure (protocol) for designing and selecting solvents for crystallization processes was developed.