Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G1 1XQ, UK; Centre for Continuous Manufacturing and Advanced Crystallisation (CMAC), University of Strathclyde, Glasgow G1 1RD, UK.
Department of Chemical Engineering, University College London, London WC1E 7JE, UK.
Int J Pharm. 2023 Mar 25;635:122691. doi: 10.1016/j.ijpharm.2023.122691. Epub 2023 Feb 8.
Consistent powder micro-feeding (<100 g/h) is a significant challenge in manufacturing solid oral dosage forms. The low dose feeding can well control the content consistency of the dosage forms, which improves drug efficiency and reduces manufacturing waste. Current commercial micro-feeders are limited in their ability to feed < 20 g/h of cohesive (i.e. powders of poor flowability) active pharmaceutical ingredients (API) and excipients (e.g. lubricants) with low fluctuation. To breach this gap, this study presents an advanced micro-feeder design capable of feeding a range of pharmaceutical-grade powders consistently at flow rates as low as 0.7 g/h with <20 % flow rate variation. This was possible due to a novel powder conveying concept utilising particle re-entrainment to minimise flow rate variations. This work details the design of this pneumatic micro-feeder and its excellent micro-feeding performance even for cohesive powders. The experimental studies investigated the influence of the process parameters (air pressure and air flow rate) and equipment configurations (insert size and plug position) on the feeding performance of different pharmaceutical-relevant powders, i.e., microcrystalline cellulose (MCC), croscarmellose sodium (CCS), crospovidone (XPVP) and paracetamol (APAP). It was shown that the system is capable of delivering consistent powder flow rates with good repeatability and stability.
在制造固体口服剂型时,实现持续的粉末微量进料(<100g/h)是一项重大挑战。低剂量进料可以很好地控制剂型的含量一致性,从而提高药物效率并减少制造浪费。目前的商业微量进料器在进料<20g/h 的粘性(即流动性差的粉末)活性药物成分(API)和赋形剂(例如润滑剂)方面的能力有限,波动较小。为了克服这一差距,本研究提出了一种先进的微量进料器设计,能够以低至 0.7g/h 的流速持续进料各种医药级粉末,流速变化<20%。这是由于采用了一种新颖的粉末输送概念,利用颗粒再夹带来最小化流速变化。这项工作详细介绍了这种气动微量进料器的设计及其出色的微量进料性能,即使对于粘性粉末也是如此。实验研究考察了工艺参数(气压和空气流量)和设备配置(插入件尺寸和堵塞位置)对不同医药相关粉末(即微晶纤维素(MCC)、交联羧甲纤维素钠(CCS)、交联聚维酮(XPVP)和对乙酰氨基酚(APAP))进料性能的影响。结果表明,该系统能够以良好的重复性和稳定性输送一致的粉末流速。