Navigate evolving API crystallization challenges driven by changing molecular properties

The continuous drive to develop drugs with improved efficacy and safety had resulted in changes in molecular descriptors of drug candidates in the last two decades. An increasing number of drug candidates with higher molecular weight, increased lipophilicity, greater restricted flexibility, are transitioning from drug discovery to drug development. This shift in molecular descriptor has been correlated with declining solubility and crystallization tendency. Crystallization of Active Pharmaceutical Ingredients: Practical Approaches, Advances, and Trends addresses these emerging difficulties, providing strategies that align crystallization objectives with evolving drug development phases while targeting growing ambitious sustainability objectives, and managing drug attrition risks and development costs.

The book examines evolving complex polymorphic landscape assessment and solid form selection, growing occurrence of oiling out and gelation phenomena, declining solubility-related obstacles, purification by solution crystallization, and reviews emerging particle formation technologies including crystallization of large biomolecules. Coverage extends to process sustainability goals targeting waste and carbon footprint reduction, digital transformation through modeling and simulation, and strategic resourcing through alliances and partnerships.

Key topics also include:

• Crystallization process design, scale-up, and scale-down methodologies applicable across pharmaceutical, fine chemical, and energy storage operations
• How increasing process sustainability requirements create additional constraints on crystallization development workflows and solvent selection decisions
• Evolution of crystallization deliverables across drug development phases to balance quality attributes against attrition risk and cost
• Strategic business considerations such as externalization, in-licensing, and partnership models for drug substance crystallization resourcing
• Projected future trends in API particle formation processes, technologies, materials, and operational approaches

Designed for chemical engineers and chemists involved in development, scale-up, or operation of crystallization processes in pharmaceutical, fine chemical, and energy storage industries, this book connects current trends in molecular properties to recent challenges to crystallization development, and reviews approaches and strategies published in recent literature to t address those challenges from both technical and business dimensions of drug substance development.

Lotfi Derdour, PhD, is an Associate Director and the US portfolio crystallization leader at GlaxoSmithKline. With over 22 years of experience in API process development focused on particle formation and isolation, he has published 20 original research articles in crystallization and drying and authored 6 patents in crystallization and solid state. He is an active member of the AIChE crystallization/evaporation scientific organizing group.