Effect of Hydration-State Variability on the Solid-State Characterization of a Pharmaceutical Non-Stoichiometric Hydrate

Roxana Schlam, Materials Science & Engineering, Drug Product Science & Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, U.S.A. (roxana.schlam@bms.com)

The solid-state characterization data of an active pharmaceutical ingredient, BMS-A, showed variability by several analytical techniques.  A comprehensive study was done with the objective to understand the behavior of this material, and how it relates to the observed analytical variability.  The data revealed that the manufacturing process consistently produces a crystalline non-stoichiometric hydrate form (HY/DHY) of the drug substance BMS-A.  The hydration state of the crystalline form can vary from zero moles of water (completely dehydrated, DHY) to one mole of water (completely hydrated, HY) as a single phase.  The non-stoichiometric hydrate nature of the form was confirmed by a number of techniques, including PXRD, ssNMR and Raman, with samples exposed to various conditions of humidity and/or temperature.  The full characterization of the form and its non-stoichiometric nature are described in detail, and a correlation between distinct features from each analytical technique and relative humidity are shown.  It was concluded that the non-stoichiometric hydrate nature of the crystalline form was the source of the analytical variability.

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Abstract Reference & Short Personal Biography of Presenting Author

Dr. Roxana F. Schlam received her B.Sc. in Chemistry from Hebrew University in Jerusalem, Israel and graduated with a Ph.D. in Chemistry from Brandeis University in Waltham, Massachusetts in the United States where she focused on structure/reactivity relationships in the solid state under Professor Bruce Foxman. She also did a postdoc at Purdue University in Indiana with Professors Stephen Byrn and Kenneth Morris where she applied her crystallography knowledge and learned about solid-state properties of active pharmaceutical ingredients and the pharmaceutical industry. Dr. Schlam started her career in the industry in the Solid-State Science group at Searle which became Pharmacia and then Pfizer.After five years, Dr. Schlam moved to New Jersey to work in the Materials Science and Engineering group at Bristol-Myers Squibb where she has been for almost 16 years.  Dr. Schlam’s research interests include the study of thermodynamics in solid-state systems and understanding bulk properties at the molecular level. Dr. Schlam holds numerous patents, scientific publications and presentations in the solid-state field of pharmaceuticals and also has extensive experience on intellectual property of crystalline forms.  Dr. Schlam is also an Adjunct Full Professor at Long Island University College of Pharmacy and Health Sciences where she lectures at the graduate level an Introduction to Solids and also Polymorphism and Hydrates: Systems, Stability and Analysis.