Crystallization of Pharmaceuticals, Design, Control, and Delivery

本研究计划涉及两个创新的连续结晶器的设计和控制，多晶型筛选平台的开发，用于活性药物成分（API）的溶解度预测的软件包，以及药物的递送系统。拟议研究计划的长期目标是从解决方案中优化API的生产，以提供安全，稳定和经济的处方药，对人体的副作用最小，对环境的影响最小。 未来五年的具体研究目标包括新型连续管式结晶器和反应性多相鼓泡塔结晶器的设计、开发、建模和控制;选定的商业重要原料药的多晶型筛选和共晶形成;主要原料药的溶解度预测和溶剂筛选，从而开发出用户-该软件包具有市场上主要API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API用于癌症治疗。 该提案将导致重要的未来交付成果：使制药行业转向连续处理模式以最大限度地降低成本和产品可变性，通过减少有机溶剂的使用来保护环境，通过分离API的更可溶的多晶型物或共晶来确保更高的药物生物利用度，以及通过仅靶向癌细胞来减少癌症药物的副作用。 拟议的研究计划为开展创新研究和培养高素质人才提供了良好的环境。第一个目标是开发和优化用于连续生产药物的新型管式冷却/反溶剂结晶器和反应性多相鼓泡塔结晶器。第二个目标提供了一个系统的程序的多晶型筛选的原料药，第三个目标导致开发的软件包的最佳选择的溶剂或溶剂混合物的结晶的昂贵的药物，和第四个目标导致开发的创新的双重靶向Fe 3 O 4核/功能化的聚合物壳纳米粒子的癌症药物的交付。该研究计划为生产和提供更好，更稳定的固态药物提供了新的方法，并培训了有能力的研究人员。

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.