Abstract

While crystalline active pharmaceutical ingredients (APIs) present good thermal stability and are easy to manufacture, amorphous APIs offer the best solution for drugs with poor solubility profile. The elucidation of solid-state molecular organization of amorphous APIs is a key step to understand their physicochemical properties and ultimately design better formulation strategies to bring poorly soluble drugs into the market. Powder X-ray diffraction is now a powerful technique to solve the structure of crystalline systems, in those cases where crystals, suitable for single crystal X-ray diffraction, are difficult to obtain. However, the challenges increase when trying to elucidate the ‘structure’ of amorphous APIs. There are no routine and direct techniques to provide a complete structural information. This raises a question: How can we obtain information about the molecular-level organization of amorphous APIs? In this presentation, I will take you to a journey into the world of both crystalline and amorphous pharmaceuticals by elucidating the strategies to be used in their structural characterization. I will present case-studies focused on three main scientific topics: i) use of in-situ and ex-situ powder X-ray diffraction to study the kinetics of API co-crystallizations and organic reactions; ii) structure solution of multicomponent crystalline APIs presenting ambiguities (co-crystals vs salts); and iii) molecular-level elucidation of amorphous APIs and investigation of polyamorphism (more than one amorphous form)

Bio

Inês C. B. Martins graduated in applied chemistry – Organic chemistry from New University of Lisbon in 2011. She did her Master´s project on multicomponent pharmaceutical systems at Instituto Superior Técnico (University of Lisbon) where she continued as a PhD student. Her thesis was focused on using combined solid-state structural techniques (powder X-ray diffraction (PXRD) and solid-state NMR) with computational methods (density functional theory calculations) to solve the structure of complex crystalline multicomponent pharmaceutical systems prepared by ball mill grinding (mechanochemistry). After completing her PhD (September 2018), she was enrolled as an Adolf Martens fellow, during 2-years, at the Federal Institute for Materials Research and Testing (BAM), Berlin, Germany. She has used in-situ methods (PXRD collected at synchrotron facilities such as Bessy II in Berlin and DESY in Hamburg, and Raman spectroscopy) to study the kinetics of organic reactions and co-crystallizations performed by ball mill grinding. Inês is currently a Postdoctoral Researcher in the Solid State Pharmaceutics group at the Department of Pharmacy, University of Copenhagen, Denmark. She is investigating a complex and barely known solid-state phenomenon termed polyamorphism (more than one amorphous form). Her research is dedicated to the molecular-level elucidation of amorphous pharmaceutical systems and their polyamorphs using pair distribution function analysis and molecular dynamics simulations.