GOALI: Continuous Coating of Ultrafine Drug Particles by Heterogeneous Polymer Nucleation in a Hollow Fiber Membrane Module

GOALI：通过中空纤维膜模块中的异质聚合物成核对超细药物颗粒进行连续包衣

• 批准号: 1100622
• 负责人: Kamalesh Sirkar
• 金额: $ 34.99万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1100622&HistoricalAwards=false
• 关键词: GOALI; Continuous; Coating; Ultrafine; Drug

This Grant Opportunity for Academic Liaison with Industry (GOALI) Program award provides funding for developing a new method for continuous film coating of nano-sized drug particles to produce large amounts of individually coated particles having a desired layer of a biodegradable polymer coating. The coating method utilizes hollow fiber membrane devices employing either cooling crystallization and/or antisolvent crystallization. Both designs will enable controlled precipitation of a dissolved polymer from solution onto nanoparticles in suspension by heterogeneous polymer nucleation. A model system consisting of silica nanoparticles will be suspended in an organic solvent containing the dissolved polymer such as Eudragit or PLGA. Such a solution, with or without other additives such as surfactants to prevent agglomeration, will be subjected to polymer precipitation onto the nanoparticle surface to form an appropriate film coating. The hollow fiber devices should allow continuous processing of polymer coating of the model systems and will be tested with pharmaceutically relevant systems supplied by the industrial partner Bristol-Myers Squibb (BMS). The polymer coatings will be characterized by SEM, EDX and TEM-EELS electron microscopic techniques; mathematical models will be developed to predict the heterogeneous nucleation-driven coating processes. The polymer coating enables the drug release in a sustained/controlled manner, improves drug bioavailability and patient compliance by reducing the drug administration frequency, allows nano-sized drugs particles to overcome a mucus barrier and target specific body organs, and prevents immune cells (macrophages) from engulfing and eliminating nano-sized drug particles in the bloodstream.If successful, this research will develop a continuous, scalable, nanoparticle coating system that can produce large quantities of polymer-coated nanoparticles while operating at temperatures and pressures far closer to ambient than those relying on supercritical fluids. Such a process should find widespread application in the pharmaceutical and other industries. Working in partnership with BMS, these processes will be scaled-up and commercialization possibilities will be explored.

这个赠款机会学术联络与工业（GOALI）计划奖提供资金，用于开发一种新的方法，连续薄膜包衣的纳米尺寸的药物颗粒，以生产大量的单独包衣的颗粒具有所需的一层可生物降解的聚合物涂层。该涂布方法利用采用冷却结晶和/或抗溶剂结晶的中空纤维膜装置。这两种设计都能够通过非均相聚合物成核将溶解的聚合物从溶液中受控地沉淀到悬浮液中的纳米颗粒上。将由二氧化硅纳米颗粒组成的模型系统悬浮在含有溶解的聚合物如Eudragit或PLGA的有机溶剂中。这样的溶液，在有或没有其它添加剂如表面活性剂以防止团聚的情况下，将经受聚合物沉淀到纳米颗粒表面上以形成适当的膜包衣。中空纤维装置应允许连续处理模型系统的聚合物涂层，并将使用工业合作伙伴百时美施贵宝（BMS）提供的药学相关系统进行测试。 聚合物涂层将通过SEM，EDX和TEM-EELS电子显微镜技术进行表征;将开发数学模型来预测异质成核驱动的涂层过程。 聚合物涂层使得药物能够以持续/受控的方式释放，通过减少药物施用频率来改善药物生物利用度和患者依从性，允许纳米尺寸的药物颗粒克服粘液屏障并靶向特定的身体器官，并防止免疫细胞（巨噬细胞）吞噬和消除血液中的纳米尺寸的药物颗粒。如果成功，这项研究将开发一个连续的，可扩展的，纳米颗粒涂覆系统，其可以产生大量聚合物涂覆的纳米颗粒，同时在比依赖于超临界流体的那些更接近环境的温度和压力下操作。这种方法应该在制药和其他工业中得到广泛应用。将与房舍管理处合作，扩大这些工艺，并探索商业化的可能性。