The mechanism of the formation of enantiotropic polymorphs of carisbamate in solution crystallization

The nucleation kinetics, as a function of supersaturation level, was studied for carisbamate, a polymorphic crystalline compound, in methanol, ethanol, 2-propanol and water. The induction times in nucleation kinetics varied markedly with respect to relative supersaturation in the range 1.3–2.3. At the same relative supersaturation, the induction time for carisbamate in methanol is the shortest, increasing in order from ethanol, 2-propanol, and then water. The interfacial tensions γ between carisbamate and methanol, ethanol, 2-propanol, and water were estimated from their induction times based on nucleation theory and were found to be about 3.6, 4.1, 4.5, and 5.7 mJ/m2, respectively. These values were of same order of magnitude as those obtained from solubility data. The equation that displays the influence of interfacial tension, supersaturation and temperature on crystallization kinetics was derived, and found to be consistent with experimental observations. The mechanism of enantiotropic polymorphism for carisbamate in the solvents is illustrated. Using interfacial tension values determined for single solvents, the polymorphic form resulting from crystallization in mixed and pure solvent systems could be predicted with good accuracy.