GOALI: Tandem Computational and Experimental Combinatorics for Controlled Crystallization of Polymorphs

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

Abstract Proposal Title: GOALI: Tandem Computational and Experimental Combinatorics for Controlled Crystallization of Polymorphs Proposal Number: CTS-0233696 Principal Investigator: Michael Ward Institution: University of Minnesota The objective of the project is to develop techniques for polymorph selection and control using appropriate epitaxial substrates. Computational and experimental combinatorial techniques for polymorph discovery will be developed. The different crystal forms that molecules adopt can affect their stability and function. In the pharmaceutical industry considerable effort is expended to discover and characterize polymorphs, largely because of their impact on bioavailability and stability. These university and industrial investigators will develop a strategy for controlling polymorphism that combines geometric lattice modeling of two-dimensional epitaxy and experimental combinatorics, with the aim of identifying substrates that are effective for selective crystallization of polymorphs. A key element of this work involves the use of lattice modeling to build substrate libraries of experimentally manageable size, based on crystalline organic and inorganic materials, expected to produce specific polymorphs. Using X-ray diffraction and spectroscopic methods, these libraries will be screened for polymorph selectivity and their overall ability to improve crystallization yields. These studies will be accompanied by real-time in situ atomic force microscopy, performed directly in crystallization media on selected substrates, which will provide direct visualization of nucleation and crystal growth and confirm the role of epitaxy. The project will lead to rational and systematic control of polymorphism, elucidation of the fundamental principles governing this phenomenon, discovery of new polymorphs, new protocols for crystallization, and improved crystallization processes. The ultimate implementation of this work will provide an important tool to aid in the design and scale-up of selected crystal forms for pharmaceutical compounds. Training students in this area is vital to keeping the competitive advantage of US industry. The PIs will also provide computation tools to the community in the form of software.