- 5:20 PM

A.P.I. Crystal Engineering in Early Development

Christopher N. Nilsen, Steven Fabian, Jeffrey Grimm, Fuqiang Liu, Stephen Manzo, and Kirk Sorgi. Global Chemical & Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 1000 Rt. 202, Room S-213, Raritan, NJ 08869

Within Early Development, Chemical Development is charged with producing API with the agreed upon salt and solid state form within given timelines. To accomplish this, unit operations such as crystallization and filtration must be considered and optimized when scaling a process even when dealing with the first kilo-size batches. The optimization involves engineering a filterable solid for typically isolating the most stable solid state form. After a brief introduction to crystallization, two systems we routinely use to engineer crystals; the Focused Beam Reflectance particle chord length Measurement system (FBRM), and the Particle Vision & Measurement (PVM) video microscopy system will be introduced and examined through case studies.

A study of the Metastable Zone Width (MSZW) on an API will demonstrate the technology's usefulness in determining the optimal concentration/temperature profile for seeding crystallizations.

The conversion of another API from the di-HCl di-hydrate to the free base anhydrate was studied and optimized to produce a crystal morphology that reduced filtration times from several days to several minutes while maintaining the correct solid state form. Particle chord length distributions of a test case and a scaled case will be presented to show the reproducibility of the final particle size distribution.