Crystallization of Pharmaceuticals, Design, Control, and Delivery

药物结晶、设计、控制和交付

• 批准号: RGPIN-2016-04445
• 负责人: Rohani, Sohrab
• 金额: $ 2.77万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687080
• 关键词: Crystallization; Pharmaceuticals; Design; Control; Delivery

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.*********

本研究计划介绍了两个创新连续结晶器的设计和控制，即多态性筛选平台的开发，用于活性药物成分（API）溶解度预测的软件包（API）以及药物的输送系统。拟议的研究计划的长期目标是优化从解决方案中的API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，并且环境影响最小。 未来五年中的特定研究目标包括新型连续管状结晶器的设计，开发，建模和控制和反应性多相气泡柱结晶器；选定的商业重要API的多态性筛选和共晶形成；主要API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，该软件包具有广泛的市场和2类溶剂的数据库；以及使用体外癌细胞测试的选定API进行癌症治疗的受控/靶向输送。可变性，通过减少有机溶剂的使用来帮助环境，通过隔离API的更溶的多晶型物或共晶体来确保更高的药物生物利用度，并仅通过靶向癌细胞来减少癌症药物的副作用。************拟议的研究计划为进行创新研究和培训高素质的人员提供了一个绝佳的环境。第一个客观导致新型管状冷却/抗溶剂结晶器的发展和优化，以及用于连续生产药物的反应性多相气泡柱结晶器。第二个目标为API的多态性筛选提供了系统的过程，第三个目标导致开发一个软件包，以最佳选择溶剂或溶剂混合物，以结晶过度昂贵的药物，并且是第四个目标导管的结晶开发创新的双重靶向Fe3O4核/功能化聚合物壳纳米颗粒来递送癌症药物。该研究计划为生产和提供更好，更稳定的固态药品的生产和交付提供了新颖的方法，并培训了有能力的研究人员。***************************************