A Unique Case of Polymorphism

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

The crystal structures of the two polymorphic forms display a number of similarities.  Both forms contain dense layers of molecules with extensive hydrogen bonding/electrostatic interactions, while interactions between layers are relatively weak and the regions between layers contain large void spaces.  The PXRD patterns of the two polymorphs also display many similarities, but are easily distinguished by a few unique low angle peaks (5-10° in 2θ); where one form has peaks the other form has baseline and vice versa.  In fact, there are a whole range of related patterns with variable peak heights and widths, again, mainly in the range 5-10° 2θ.  Based on single crystal diffraction data and powder pattern indexing, the diversity of patterns is most likely caused by layer stacking faults.  Additional studies using other characterization techniques did not show significant differences between the two forms. In the course of determining the thermodynamic relationships, it was noted that slurries containing both forms are very sluggish to convert to the more stable form. However, due to the close structural and thermodynamic relationship between the polymorphs, phase purity is not expected to have a significant impact on the performance of drug product.

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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.