One aspect often overlooked in API development is the pivotal role of choosing the adequate solvents. This is even more crucial when dealing with solid formulations, where choosing an appropriate solvent is the cornerstone of good crystallization development. The solvent system from which an API is crystallized, influences solubility, growth and nucleation kinetics, impurity purging, polymorph control, solvation propensity and crystal morphology. Despite the importance of this choice, in early phase development, solvents are typically chosen based on chemical intuition with only the impact of product yield considered. This can lead to insufficient purity, unfavourable particle size and serious processability issues in later phases of both drug substance and drug product development. Using predictive modelling and smart experimentation, one can select optimal solvents for process development across eight criteria: yield, productivity, antisolvent efficiency, solvation and oiling propensity, impurity rejection, seed ability and safety and environmental choices.
Understanding the role of the solvent in your crystallization system is critical for any API development. Crystal16 and Crystalline devices aid you in the solvent selection process in the early stages of pharmaceutical crystallization process development in a quick and cost-effective manner. This is done by using several small-scale parallel crystallizers up to 5 mL scale in the case of Crystalline. This experimental approach allows for the determination and study of solubility curves, MSZW, effect of additives, nucleation rate and other aspects related to crystallization, while speeding up development time and minimizing material consumption at larger scales.