Shape Engineering of Organic Crystals

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

Proposal Number: CTS-0411630 Principal Investigator: Michael Doherty Institution: University of California-Santa Barbara The goal of the proposed research is to develop a new generation of modeling tools for the growth and dissolution of organic crystals. The models will allow quantitative predictions to be made for solution-mediated polymorphism and the simultaneous prediction of particle size and shape of organic crystals grown from solution. The specific tasks include the development of a dynamic model to predict the evolution of crystal shape during growth and dissolution, the development of fundamental growth and dissolution models for crystal faces that account for the influence of solvent on the face growth/dissolution rates, and the integration of these models with population balance models to simultaneously predict size and shape of organic crystals grown from solution. Crystallizer experiments are proposed to validate the key predictive aspects of the approach. Model systems will include carboxylic acids and amino acids grown from aqueous and organic solvents. One aspect of this research will be to provide the necessary coupling between crystal chemistry and crystallizer engineering design. The broader impact of this work will be to show that solid-state chemistry can be coupled with engineering principles. This project will have an impact on chemical engineering education through the potential for new course offerings and textbooks. This work could have a large impact on the pharmaceutical industry, where most products are formulated in particulate, crystalline form. Reviewers recognized the importance of the work and the ability of the PI to perform the research. The PI has the ability to integrate solid-state chemistry, interface structure, and modeling algorithms. The research will address the important problem of polymorphism. This will be challenging, as polymorphism is sensitive to heterogeneous nucleation, solvent, temperature, super saturation, and impurities. The connection of the modeling with a laboratory crystallizer is a plus and will ensure the proper feedback between modeling and experiment. Successful completion of the project would have broad impacts on the way crystal growth is viewed. It could represent a significant advance in the ability to predict crystal shape and the effects of additives and solvents on morphology.