GOALI: Fundamental Material and Processing Studies on Hot-Melt Extrusion-A Novel Pharmaceutical Manufacturing Process

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。该奖项的研究目标是开发一种基于热熔挤出（HME）的通用和新型药物制造技术，该工艺具有提高难溶性药物生物利用度的潜力。HME将被视为一个多学科领域，需要制药和聚合物科学以及聚合物加工的基础知识和专业知识。该研究将解决两个基本的、实际上重要的问题：1）如何选择或设计合适的聚合物赋形剂与具有较差水溶性的药物混合，使得药物可以具有加速的释放速率和/或改善在水中的溶解度？2)活性药物成分（API）和聚合物辅料如何在挤出机内混合？将选择一系列赋形剂，包括聚合物-纳米粘土组合，并用模型药物进行测试，以研究它们的相容性和相互作用。挤出过程将使用在线和离线工具进行研究。可交付成果包括基本混合机制的目录，稳定性/相容性和加工结果的分析和建模，以及学术和工业实验室的工程学生教育。如果成功，这项研究的结果将对制药行业产生重大的、潜在的变革性影响。这些结果将有助于使许多因溶解度导致生物利用度差而从未进入市场的药物商业化，并将一些药物的给药途径从注射改为口服。这两个变化将通过大幅削减成本和增加新药管道来帮助制药行业。对药物-赋形剂相容性和挤出工艺的基本理解也将影响其他行业，例如医疗器械和食品行业，因为也可以应用相同的混合和挤出工艺。研究生和本科生将受益于NJIT/PPI和惠氏实验室的实践研究经验，以及即将开发的新制药工程课程。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). The research objective of this Grant Opportunity for Academic Liaison with Industry (GOALI) award is to develop a general and novel drug manufacturing technology based on Hot-Melt Extrusion (HME), a process that holds the potential of improving the bioavailabilty of poorly soluble drugs. HME will be treated as a multidisciplinary field, requiring fundamental knowledge and expertise from pharmaceutical and polymer science, and polymer processing. The research will address two fundamental, practically important, questions: 1) How to select or design appropriate polymeric excipients to mix with drugs that have poor water solubility so that the drugs can have accelerated release rate and/or improved solubility in water? 2) How do the Active Pharmaceutical Ingredients (API) and the polymeric excipients get mixed inside the extruder? A series of excipients, including polymer- nanoclay combinations, will be selected, and tested with model drugs to investigate their miscibilities and interactions. The extrusion process will be studied using on-line and off-line tools. The deliverables include a catalog of basic mixing mechanisms, analysis and modeling of stability/miscibility and processing results, and engineering student education at both academic and industry laboratories. If successful, the results of this research will bring significant, potentially transformative, impact on the pharmaceutical industry. The results will help to commercialize numerous drugs that never went to the market place due to their solubility-caused poor bioavailability, and change the delivery route of some drugs from injection to oral. Both changes will assist the pharmaceutical industry by dramatically cutting costs and increasing the new drug pipeline. The fundamental understanding of the drug-excipient miscibility and the extrusion process will impact other industries as well, such as the medical device and food industries, since the same mixing and extrusion processes can also be applied. Graduate and undergraduate students will benefit from the hands-on research experience at NJIT/PPI and Wyeth laboratories, and also from the new pharmaceutical engineering courses to be developed.