Determining the Growth Mechanism of Tolazamide by Induction Time Measurement

A turbidity measurement-based experimental method for the determination of the crystallization induction period is described. The induction times for crystallization of tolazamide, an oral hypoglycemic agent, were measured over a range of supersaturation in both unseeded and seeded crystallization experiments. The measured induction times were then treated using the expressions developed by van der Leeden et al., which relates the induction time and the supersaturation for various growth mechanisms in unseeded and seeded crystallization. On the basis of these analyses, the growth mechanism of tolazamide was identified as two-dimensional nucleation-mediated growth. The analyses also afforded estimation of the kinetic parameters such as nucleation and growth rate constants. In addition, atomic force microscopy imaging of the major faces of tolazamide crystals corroborated this growth mechanism.