title: An approach to solvent screening for crystallization of polymorphic pharmaceuticals and fine chemicals.
abstract: It is desirable to have a systematic approach for predicting or interpreting the effect of the solvents on the production of polymorphs. A method based on the atomic electronegativity is suggested that calculates the partial charge distribution in the solute and solvent molecules. Using the calculated partial charges, correlations are developed to predict the hydrogen bonding ability of the solute and/or solvent molecules. The predictive capability of the proposed correlations is compared with the results of a quantum mechanics approach. Selection of the right solvent may play a significant role in the formation of a desirable polymorph or solvate. The most important properties of class 2 and 3 solvents of International Conference on Harmonization (ICH) for crystallization of polymorphic compounds are listed in this paper. The partial charge calculation has been used as a tool for analyzing the solvent impact on polymorphic isolation of two compounds: ranitidine hydrochloride (H2 receptor antagonist) and stearic acid (used as excipients or in coating the tablets).
authors.affiliation: Chemical and Biochemical Engineering Department, The University of Western Ontario, London, Ontario, Canada, N6A 5B9 Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mirmehrabi
authors.forename: Sohrab
authors.initials: S
authors.lastname: Rohani
mesh_terms: D000465:Algorithms; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry; D003460:Crystallization; D004563:Electrochemistry; D006860:Hydrogen Bonding; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011899:Ranitidine / Q000008:administration & dosage / Q000737:chemistry; D012997:Solvents; D013229:Stearic Acids / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000897:Anti-Ulcer Agents; D004364:Pharmaceutical Preparations; D012997:Solvents; D013229:Stearic Acids; C031183:stearic acid; D011899:Ranitidine