Fundamentals of Solid Formulation

Maxwell W. Terban graduated from the University of Massachusetts Amherst in 2012 with a B.S. in chemical engineering. He earned a Ph.D. in materials science and engineering from Columbia University in New York City in 2018, focused on characterizing disordered materials using x-ray scattering techniques. He currently resides in Stuttgart, Germany where he works as a scientist at the Max Planck Institute for Solid State Research in the X-ray Diffraction group. His research investigates the formation and structure−property relationships of functional materials including nanomaterials, polymers, small molecules, and microporous compounds.

Nanoparticulate; disordered; amorphous; these are terms increasingly used to describe new technological materials. However, the optimization of material properties is often not conducive to structural understanding. In search of higher surface areas or better solubilities, the generation of nanoparticulate and noncrystalline products gives a black box into which the standard procedures of x-ray crystallography do not easily see. We are left wanting for an aid to product structure identification. How can we obtain deeper insights into why different processing procedures result in different physicochemical properties? How can we rationalize the mechanisms involved in the materials formation or action? In this talk, I will give my perspective on local structural ordering in noncrystalline molecular materials. I will briefly introduce the methods of total scattering and atomic pair distribution function analysis as tools to access this information, and then give an overview of examples including the effects of amorphization method on pharmaceutical and excipient compounds and formulation in polymer blends. Further use cases touched upon will include identifying molecular motifs, signatures of binding interactions, and structure determination.

Eric Dybeck is a Senior Principal Scientist at Pfizer in the Machine Learning and Computational Sciences department. He received a B.S. in Chemical Engineering from Bucknell University and a Ph.D. in Chemical Engineering from the University of Virginia. At Pfizer, Eric develops and implements computational workflows to support various aspects of drug design and development including lead optimization, process development, and solid form selection.

The transformation of a pharmaceutical solid from an anhydrous crystal into a hydrated form during drug development represents a risk to a product’s safety and efficacy due to the potential impact on stability, bioavailability, and manufacturability. Hydrates tend to form under conditions of high humidity and/or low temperature. In this work, we explore various molecular modeling techniques to generate the temperature-humidity phase diagram of pharmaceutical anhydrous-hydrate pairs and show how these diagrams can be used to assist with process development, solid form selection, and recommended storage conditions.