Tablet and Particle Attrition in Pharmaceutical Processes

美国国家科学基金会-化学与运输系统分部-颗粒与多相过程项目（1415）摘要提案编号：0625792首席研究员：Wassgren， Carl r .合作单位：普渡大学提案标题：制药过程中片剂和颗粒的磨损智力价值拟议的工作将研究制药过程中片剂的磨损，具体而言，用于预测混合和包衣操作过程中药片和颗粒损伤的离散元模型（DEM）计算机模拟中嵌入的磨损子模型的准确性将通过实验测试进行评估，以更好地估计常见药物加工操作中药片和颗粒的磨损程度。此外，还将对如何修改材料特性（如形状和表面硬度）以及操作条件（如搅拌机速度和混合元件设计）提出建议，以便将片剂和颗粒磨损降至最低。这些目标将通过进行实验和相应的三维软颗粒DEM模拟来实现，其中分别记录片剂在标准脆性测试仪中的质量损失和表面损伤，片剂和颗粒在旋转圆柱形滚筒中，片剂和颗粒在平底锅涂布机和v型搅拌机中。将实验和计算机模型之间的磨损程度和方法进行比较，以确定哪些磨损子模型最准确地描述常见药物加工操作中的片剂和颗粒损伤。本提案中概述的工作将使人们更好地理解在制药、食品和农用化学工业中发现的常见单元操作中作用于颗粒的重要磨损机制，设计和控制单元操作的计算工具，以便将磨损降至最低，测试程序和设备将准确评估常见单元操作中材料的磨损程度。并对设备、操作程序和材料进行设计修改，以减少磨损损害。更广泛地说，这项工作将大大减少在广泛的工业中由于材料损坏而造成的材料损失，并减少由磨损引起的粉尘形成所造成的健康和环境风险。该结果也有望使采矿和铣削社区受益，其中需要颗粒磨损以减小颗粒尺寸。

National Science Foundation - Division of Chemical &Transport Systems - Particulate & Multiphase Processes Program (1415)ABSTRACTProposal Number: 0625792Principal Investigator: Wassgren, Carl R.Affiliation: Purdue UniversityProposal Title: Tablet and Particle Attrition in Pharmaceutical ProcessesIntellectual MeritThe proposed work will study the attrition of tablets in pharmaceutical processes, specifically the accuracy of attrition sub-models embedded within discrete element model (DEM) computer simulations for predicting pharmaceutical tablet and particle damage during blending and coating operations will be evaluated by experimental testing to better estimate the degree of attrition of pharmaceutical tablets and particles in common pharmaceutical processing operations. Additionally, recommendations will be made for how to modify material properties, such as shape and surface hardness, and operating conditions, such as blender speed and mixing element design, so that tablet and particle attrition may be minimized. These objectives will be achieved by conducting experiments and corresponding 3D soft-particle DEM simulations in which the mass loss and surface damage are recorded for tablets in a standard friability tester, tablets and particles in a rotating cylindrical drum, and tablets and particles in a pan coater and V-blender, respectively. The degree and method of attrition will be compared between the experiments and computer models to determine which attrition sub-models are most accurate at describing tablet and particle damage during common pharmaceutical processing operations.Broader ImpactsThe work outlined in this proposal will result in an improved understanding of the significant attrition mechanisms acting on particles during common unit operations found in the pharmaceutical, food, and agro-chemical industries, computational tools for designing and controlling unit operations so that attrition may be minimized, testing procedures and equipment that will accurately assess the degree of attrition for materials in common unit operations, and design modifications to equipment, operational procedures, and materials to reduce attrition damage. More broadly, this work will significantly reduce the material losses incurred due to material damage in a wide range of industries as well as reduce the health and environmental risks resulting from the formation of the dust caused by attrition. The results are also expected to benefit the mining and milling community where particle attrition is desired to reduce particle size.