Solubility Metastable Zone Width Measurement and Crystal Growth of the 1:1 Benzoic Acid/Isonicotinamide Cocrystal in Solutions of Variable Stoichiometry

ABSTRACTThe solubility and crystal growth of the 1:1 cocrystal between benzoic acid and isonicotinamide from 95% ethanol was studied through the creation of a ternary phase diagram at differing temperatures and turbidity measurements. From the solubility measurements thermodynamic properties of the system were evaluated, which indicate little solution binding of the two components supported by in situ FT-IR spectra. Cooling crystallisation from solutions of differing composition suggests differing crystal growth characteristics. An excess of benzoic acid appears to increase the metastable zone width and reduce the crystal size through interactions along the fastest growth axis, while an excess of isonicotinamide decreases the metastable zone width with increased crystal size. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3826–3838, 2010