(310b) Polymorphism in Drug Compounds By Controlling Fluid Dynamics during Crystallization

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. We are able to isolate polymorphs using small amounts (micrograms) of material. This is ideal because small batches of material are sufficient to obtain multiple polymorphs of drug candidate molecules without consuming a lot of the material. Finally, when we create the polymorphs as thin films, we can also use these polymorphs for further study of candidate drug performance, for example, testing for solubility and bioavailability being relevant to pharmaceuticals. With continued study and development of this technology, implementation in industry can allow for rapid search of the polymorphic space during drug development.