Crystal growth kinetics of a metastable polymorph of Tolbutamide in organic solvents

The crystal growth of tolbutamide (Form IL) in different solvents has been investigated by isothermal seeded desupersaturation experiments at different temperatures (268-283 K). Experimental data has been evaluated using empirical power law equations and the mechanistic based models: Burton-Cabrera-Frank (BCF) and Birth and Spread (B+S). The estimated activation energies and growth exponents suggest a surface integration controlled growth as confirmed separately by a mass transfer analysis. From the B+S model, the estimated solid-liquid interfacial energies and the mean diffusion distances on the surface ranged 1.23-1.90 mJ/m2 and 1-16 nm, respectively. The growth rate is strongly dependent on the solvent, decreasing in the order: acetonitrile > ethanol > ethyl acetate > n-propanol > toluene. The crystal growth becomes slower as the overall strength of the solute-solvent binding increases. This influence of the solvent corresponds very well with that found for nucleation of tolbutamide in the same solvent...