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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615066
• 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.

目前的研究项目涉及两种创新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）溶解度预测的软件包以及药物输送系统。拟议研究计划的长期目标是优化原料药的生产，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。未来五年的具体研究目标包括新型连续管式结晶器和反应多相鼓泡塔结晶器的设计、开发、建模和控制；选定的商业上重要的 API 的多晶型筛选和共晶形成；主要 API 的溶解度预测和溶剂筛选，从而开发出用户友好的软件包，其中包含市场上主要 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/靶向输送选定的用于癌症治疗的 API。 该提案将带来重要的未来交付成果：使制药行业能够转向连续加工模式，以最大限度地降低成本和产品变异性，通过减少有机溶剂的使用来帮助环境，通过分离更可溶的多晶型物来确保更高的药物生物利用度或 API 的共晶体，并通过仅针对癌细胞来减少抗癌药物的副作用。 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品的新型管式冷却/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 API 多晶型筛选的系统程序，第三个目标导致开发软件包，用于最佳选择用于结晶昂贵药物的溶剂或溶剂混合物，第四个目标导致开发软件包开发用于输送癌症药物的创新双靶向 Fe3O4 核/功能化聚合物壳纳米颗粒。该研究项目为生产和提供更好、更稳定的固态药物以及培训有能力的研究人员提供了新方法。