PROPOSAL NUMBER: CBET- 0651711 PRINCIPAL INVESTIGATOR: Michael Doherty AFFILIATION: University of California Santa Barbara PROPOSAL TITLE: Crystallization of Active Pharmaceutical Ingredients
The goal of the proposed research is to develop a new generation of modeling tools, supported by experiments, for the growth and dissolution of organic crystals, especially active pharmaceutical ingredients (API's). The new generation of models will allow quantitative predictions to be made for the shape of organic crystals grown from solution and for solution mediated polymorphism. The specific tasks include the development of fundamental growth and dissolution models for crystal faces that account for the influence of complex bond chains (caused by the size and structure of API molecules) and solvent on the face growth/dissolution rates. Crystallization experiments are proposed to validate the key predictive aspects of the approach. Model systems will include paracetamol (acetaminophen), Lovastatin (a cholesterol lowering drug), and amino acids grown from aqueous and organic solvents. The intellectual merit, and main contribution of this research program will be to provide a strong coupling between crystal chemistry and crystal engineering for improved product and process design. The major benefit will be more reliable, high fidelity, predictive models that will reduce research and development times for crystallization product and process technology. The proposed research program is geared towards the development of quantitative, predictive, engineering design models that harness the vast amounts of descriptive literature information about crystals so that improved engineering systems can be designed. The broader impact of this work will be to show that solid state chemistry can be coupled with engineering principles. Success will have an impact on chemical engineering education through the potential for new course offerings and textbooks. It will also have an impact on industrial R&D work practices. Graduate research assistants will be educated in this important area, and they will help to transfer the technology to industry.
