Crystallization Monitoring of Active Pharmaceutical Ingredient By Raman Spectros - Seguridad Mania.com - España y América Latina

Full Title: Crystallization Monitoring of Active Pharmaceutical Ingredient By Raman Spectroscopy Presented by John-David McElderry, Scientist at Biogen Crystallization of active pharmaceutical ingredients (API) as a process of purification, final crystal form selection, and/or particle size control is an important step in pharmaceutical manufacturing processes. Some crystallizations exhibit high degrees of complexity, making process development optimization and control challenging. In this study, Raman spectroscopy was utilized to monitor in real-time the polymorph form transition (Polymorphic form change: A → B → C) of an API in development at Biogen. Using polymorph reference materials, a multivariate approach was developed to identify the in-situ crystalline form of the API during the crystallization. The process started by dissolving API in dichloromethane in a jacketed lab reactor. A distillation was then performed to reduce the water content. Then a constant-volume distillation was implemented removing dichloromethane while iso-propanol was added (Polymorphic form nucleation of A). After all the dichloromethane was removed, seeds of the target form (C) were added and the mixture was held overnight. The real-time identification approach was capable of detecting the final form change (A → B → C or A → C).