Crystallization of Pharmaceuticals, Design, Control, and Delivery

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The present research program deals with the design and control of two innovative continuous crystallizers, the development of a polymorphic screening platform, a software package for the solubility prediction of active pharmaceutical ingredients (APIs), and a delivery system for the pharmaceuticals. The long-term objective of the proposed research program is to optimize the production of APIs from a solution to provide safe, stable, and economical prescription drugs with minimum side effects in the human body and minimum environmental impact. The specific research objectives in the next five years include the design, development, modeling and control of a novel continuous tubular crystallizer and a reactive multi-phase bubble column crystallizer; the polymorphic screening and cocrystal formation of a selected commercially important APIs; the solubility prediction and solvent screening of major APIs leading to the development of a user-friendly software package with an extensive data base of the major APIs in the market and the class 2 solvents; and the controlled/targeted delivery of selected APIs for cancer therapy using in vitro cancer cells tests. This proposal will lead to significant future deliverables to: enable the pharmaceutical industry to switch to the continuous processing mode to minimize the cost and product variability, help the environment by reducing the use of organic solvents, secure higher drug bioavailability by isolating the more soluble polymorph or cocrystal of an API, and reduce the side effects of a cancer drug by targeting only the cancer cells. The proposed research program provides an excellent environment to conduct innovative research and train highly qualified personnel. The first objective leads to the development and optimization of a novel tubular cooling/anti-solvent crystallizer and a reactive multi-phase bubble column crystallizer for the continuous production of pharmaceuticals. The second objective provides a systematic procedure for the polymorphic screening of the APIs, the third objective leads to the development of a software package for the optimal selection of a solvent or a solvent mixture for the crystallization of prohibitively expensive pharmaceuticals, and the fourth objective leads to the development of an innovative double targeting Fe3O4 core/functionalized polymer shell nanoparticle for the delivery of cancer drugs. The research program offers novel approaches for the production and delivery of better and more stable solid state pharmaceuticals, and training of competent researchers.