Department of Chemical Engineering, California State University, Long Beach, California, USA.
Department of Chemical and Biochemical Engineering. Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
AAPS PharmSciTech. 2019 Jul 23;20(7):262. doi: 10.1208/s12249-019-1473-1.
Continuous manufacturing (CM) has clear potential for manufacturing solid oral dosages. It provides several advantages that may aid the manufacturing and quality of drug products. However, one of the main challenges of this technology is the relatively large amount of knowledge required and the amounts of material needed to develop the process during the early stages of development. Early process development evaluations of continuous manufacturing equipment often require larger amounts of material compared with batch, which hinder CM prospect for drugs during the early stages of process development. In this work, a small-scale evaluation of the mixing process occurring in a continuous mixing system was performed. The evaluation involved the use of a small-scale "mixing cell" which was able to replicate the lubrication process of a continuous mixer. It is worth mentioning that we designed the mixing cell by reconfiguration of an existing continuous tubular blender. The extent of lubrication evaluation was performed for three example formulations and was done by mimicking the amount of shear provided to a formulation by means of matching the number of paddle-passes that a formulation experiences within a continuous blending process in the batch mixing cell. The evaluation showed that the small-scale mixing cell was able to replicate the extent of lubrication-evaluated by measuring the tensile strength of compacts being made with both the continuous and mixing cell experiments-occurring in the continuous mixer using a fraction of the amount of materials needed to perform the same evaluation in the continuous blending process.
连续制造（CM）在制造固体口服剂量方面具有明显的潜力。它提供了许多优势，可能有助于药物产品的制造和质量。然而，这项技术的主要挑战之一是在开发早期阶段需要相对大量的知识和材料来开发工艺。与批量生产相比，连续制造设备的早期工艺开发评估通常需要更多的材料，这阻碍了 CM 在药物开发的早期阶段的应用前景。在这项工作中，对连续混合系统中发生的混合过程进行了小规模评估。该评估涉及使用小型“混合单元”，该单元能够复制连续混合器的润滑过程。值得一提的是，我们通过重新配置现有的连续管状混合器来设计混合单元。通过模拟在批处理混合单元中连续混合过程中提供给配方的剪切量，来完成三种示例配方的润滑程度评估，具体做法是匹配配方在连续混合过程中经历的桨叶通过次数。评估结果表明，使用连续混合器中所需材料的一小部分，小型混合单元能够复制通过连续和混合单元实验测量的压缩强度来评估的润滑程度，从而评估发生在连续混合器中的润滑程度。
