Crystallization of Pharmaceuticals, Design, Control, and Delivery

目前的研究项目涉及两个创新连续结晶器的设计和控制，多态筛选平台的开发，用于活性药物成分（api）溶解度预测的软件包，以及药物的输送系统。拟议研究计划的长期目标是优化原料药的生产，以提供安全、稳定、经济的处方药，对人体的副作用最小，对环境的影响最小。未来5年的具体研究目标包括：新型连续管式结晶器和反应式多相泡塔结晶器的设计、开发、建模和控制；选定的具有重要商业价值的原料药的多态筛选和共晶形成；主要原料药的溶解度预测和溶剂筛选，从而开发了一个用户友好的软件包，其中包含市场上主要原料药和2类溶剂的广泛数据库；以及使用体外癌细胞测试控制/靶向递送选定的原料药用于癌症治疗。

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.