Small-molecule active pharmaceutical ingredients (APIs) are known to be capable of crystallizing in multiple lattice structures, a property known as polymorphism. An understanding of the physico‑chemical properties of these crystalline solid forms (including their solubility, hygrocsopicity, solvation state, morphology, and stability) is pivotal to being able to select the optimal solid form for further development.
This webinar presents an approach to optimizing the solid form of an API. The process starts on the milligram scale in high-throughput polymorphism, salt, and co-crystal screenings. The resulting leads are scaled-up to permit full characterization of each crystal form and to elucidate the interrelationships among polymorphs (including solvates and hydrates). Once a solid form with the desired properties has been identified, crystallization processes can be optimized on a 100–400-mL scale using process analytical tools to determine suitable solvent/antisolvent ratios, seeding temperatures, seed amounts, cooling ramps, and so on in order to obtain the chosen product with a high yield and high purity. The crystallization process can then be scaled-up to the kilogram scale according to the GMP quality standard to provide material for early clinical studies. Several case studies will be presented. QA to Follow.
We will be joined by webinar speaker Susan DePaul, PhD, Team Lead, Solid-State Development Projects.
Susan M. De Paul is the Team Leader of the Solid-State Development group at Solvias AG in Switzerland. Her team specializes in contract research in the field of solid-state development of pharmaceuticals. This includes discovering crystalline forms (polymorphs) of drug substances, crystallizing multi-component systems (salts, co-crystals), characterizing the physicochemical properties of these solid forms to guide preformulation, selecting the best solid form for development, and developing a crystallization process from the mg to kg scale.
A physical chemist by training, Susan received her Ph.D. from the University of California, Berkeley in the field of solid-state NMR. She has over 20 years of experience in the crystallization of pharmaceuticals, holds approximately 10 patents, and has co-authored several chapters in books (most recently Chapter 14 in "Polymorphism in the Pharmaceutical Industry: Solid Form and Drug Development," Rolf Hilfiker & Markus von Raumer, Eds., Wiley-VCH, 2019).
Learning Objectives:
- Screening for the optimal solid form of the API
- Scaling up the optimal form of the API from miligrams to kilograms
