(495e) Effective Particle Engineering Soultion Via Continuous Crystallization

Today’s active pharmaceutical ingredients (APIs) are increasingly complex in structure and challenging for isolation. Effective API particle engineering is playing a critical role in meeting the demands for drug substance and drug product development. Although crystallization process is desired and commonly used as final isolation step for API production, there are many practical challenges from early process development to process scale-up and implementation in the plant. Some of the challenges are inherently related to the molecular structure and/or API crystal properties, such as high solvation propensity, low chemical stability, high oiling tendency, impurity/API structure similarity, etc.. Some are related to the inherent scale-up issues of batch processing, with drastic changes in mass, heat, and momentum transfers in large batch crystallizers. This talk will share case studies when continuous crystallization offers robust processing solutions to challenging APIs that are otherwise hard to isolate and produce at large scale. The process design concept will be discussed with respect to control over purity, polymorph, PSD, oiling-out, etc..