(684b) Coupling Experimental Results with Molecular Dynamics Simulations to Describe Polymorphism Obtained Using Solution Shearing

During pharmaceutical drug development, it is important to carry out an extensive search to identify all drug forms. Stabilizing metastable polymorphs is necessary to ensure that the correct drug form is selected for development to balance form stability and drug bioavailability. However, searching for rare forms is a nontrivial process. Here, we show that a combination of fluid dynamics and surface chemistry can be used to overcome some of the challenges associated with searching this extensive landscape of polymorphism. In this study, multiple forms of glycine and acetaminophen were isolated, including metastable forms that are difficult to obtain using conventional methods. The mechanisms through which multiple polymorphs are obtained are described herein. Molecular dynamics simulations and in-situ grazing incidence wide angle X-ray diffraction lend insight to the phase transitions that occur during the crystallization process for fundamental understanding of solution shearing.