Solubilities and Crystallization of Olanzapine Using a Multi-Well Setup: The Effect of Solvents and Cooling Rates

The use of a multi-well system allowed us to measure the solubility of two anhydrous forms of olanzapine in pure solvents with different polarities in a temperature range of 20 to 60° Celsius (°C) with a small quantity of material. After that, we carried out cooling crystallization experiments in a stagnant medium with a small volume of 0.8 mL and a small quantity of material. We found that the solubility increased with the solvent polarity in the order: methanol > ethanol > acetonitrile > ethyl acetate > tetrahydrofuran > toluene. We demonstrated the effect of the solvents and the cooling rates on the crystal habit, crystal phase, and crystal size distribution.