ABSTRACT: Crystallization is important for pharmaceuticals, amino acids, and proteins. The first part of this seminar will discuss the crystallization of small-molecule organic chemicals such as pharmaceuticals and amino acids. The crystal size distribution (CSD) can affect the efficacy of drug products (such as the amount of drug reaching the lungs from a nasal spray) as well as the efficiency of downstream processes such as filtration and milling. CSD control can be challenging when the crystallization simultaneously includes many phenomena, such as growth, particle attrition and breakage, agglomeration, and secondary nucleation.
My new crystallizer designs greatly enhance the control of the crystal size distribution. One strategy is to exploit multiphase flow to decouple nucleation and growth so that these phenomena can be individually controlled. Another strategy is to increase the degrees of freedom in the dynamic operation of the crystallizers. Experimental validation has confirmed that my designs suppress secondary nucleation, attrition, and aggregation/agglomeration—dominant but undesired phenomena that worsen the ability to control the CSD in most existing crystallizer designs.
The last part of this seminar will propose some new design strategies for the crystallization of biopharmaceuticals, especially proteins, which constitute a growing proportion of new therapeutic compounds. Strategies are proposed both for the generation of single crystals for use in determining the protein structure for use in drug design, and for the generation of large quantities of protein crystals as a route towards inexpensive purification, extended shelf-life, or alternative modes of drug delivery.
Biosketch:
Mo Jiang is a Ph.D. student in chemical engineering at the Massachusetts Institute of Technology (MIT) with Prof. Richard D. Braatz in the area of pharmaceutical crystallization. He received a B.S. degree in 2006 from Tsinghua University and an M.S. degree in chemical engineering in 2008 from the University of Illinois at Urbana-Champaign. Before joining the Ph.D. program at MIT, he also interned at Abbott Laboratories and Boehringer Ingelheim Pharmaceuticals Inc., where he applied solid-state characterization, dual-impinging-jet mixers, and continuous crystal seed generation to the development of processes to generate crystals of a target size.