Smart Manufacturing of Pharmaceutics by Discrete Particle Modeling

通过离散粒子建模实现药品智能制造

• 批准号: RGPIN-2017-04693
• 负责人: Thompson, Michael
• 金额: $ 2.7万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709130
• 关键词: Smart; Manufacturing; Pharmaceutics; Discrete; Particle

The pharmaceutical sector is identified as important to Canada's high-tech economy and as a key element of Ontario's Innovation Agenda (published December 2015) which focuses on strategic areas to build employment. This sector relies heavily upon fundamental research to support its products, and is keenly in need of persons completing post-graduate studies, trained to implement their innovations. This proposal centres on pharmaceutical manufacturing' which has received increasing attention since 2004 when federal regulatory bodies, recognizing a decline in interest to manufacture drugs, recommended the industry transition from their batch unit operations to continuous processes for the sake of lower costs without jeopardizing drug quality. Solid oral dosage forms, like tablets, are still the most popular class of drugs sold and as a result, their manufacture will be the earliest adopter of continuous technologies, though very cautiously at first till the process is understood. For the majority of tableted pharmaceuticals, agglomeration of powdered ingredients into granules is the first step to final drug production. Twin-screw granulation is the newest continuous technology in the industry and is generally considered the most productive based on giving the highest consistency for the highest throughput rate. Our research group was one of three early global innovators in establishing the technologies behind twin-screw granulation, and has work closely with most major pharmaceutical companies to understand their concerns. Under the enclosed proposal we intend to once again shift our focus, away from the now increasingly busy research space of formulation development, into the sparsely covered knowledge areas of modeling the new technology. Using our last eight years of accumulated process knowledge for validation, this proposal seeks to develop a readily adaptable representation of the microscale mechanics of twin-screw granulation and then, in the short term, use that model to explain the fundamentals of the process as ingredients and configurations differ. The long term goal of the outlined research program is to combine new sensor technologies that we will devise using machine vision and acoustics, with our model of the process to devise a smart manufacturing strategy that not only identifies quality control issues but explains the causes for such deviations. The outlined five-year program will train at least six HQP in granulation, discrete particle simulations, acoustic and optical sensors, and characterization of particulate systems, giving them highly sought skills for an industry increasingly employing chemical engineers to implement its new continuous technologies.

制药部门被确定为加拿大高科技经济的重要组成部分，也是安大略省创新议程(2015年12月发布)的关键要素，该议程侧重于创造就业的战略领域。该部门在很大程度上依赖基础研究来支持其产品，并迫切需要完成研究生学习、接受培训以实施创新的人员。自2004年以来，这一提议受到越来越多的关注，当时联邦监管机构认识到制造药品的兴趣下降，建议该行业从分批单位运营转向连续生产，以便在不损害药品质量的情况下降低成本。固体口服剂型，如片剂，仍然是销售的最受欢迎的药物类别，因此，它们的生产将成为连续技术的最早采用者，尽管一开始非常谨慎，直到了解过程。对于大多数片状药物来说，将粉状成分凝聚成颗粒是最终药物生产的第一步。双螺杆造粒是行业中最新的连续制粒技术，通常被认为是生产率最高的技术，因为它提供了最高的稠度和最高的生产率。我们的研究小组是建立双螺杆造粒技术的三个早期全球创新者之一，并与大多数主要制药公司密切合作，了解他们的担忧。根据所附提案，我们打算再次将我们的重点从现在日益繁忙的配方开发研究领域转移到覆盖较少的新技术建模知识领域。利用我们过去八年积累的工艺知识进行验证，该建议寻求开发一种易于适应的双螺杆造粒微观机理的表示法，然后在短期内使用该模型来解释该工艺的基本原理，因为成分和配置不同。概述的研究计划的长期目标是将我们将利用机器视觉和声学设计的新传感器技术与我们的过程模型结合起来，设计出一种智能制造战略，不仅能识别质量控制问题，还能解释这种偏差的原因。这项概述的五年计划将在造粒、离散粒子模拟、声学和光学传感器以及颗粒系统的表征方面培训至少六名HQP，使他们获得一个越来越多地雇用化学工程师来实施其新的连续技术的行业迫切需要的技能。