University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, Kuopio, Finland.
AstraZeneca R&D, Mölndal, Sweden.
Int J Pharm. 2015 Nov 10;495(1):290-301. doi: 10.1016/j.ijpharm.2015.08.077. Epub 2015 Aug 28.
The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems.
本研究旨在探索连续干法制粉与直接压片工艺用于制备缓控释（ER）骨架片。该研究采用了具有挑战性的配方设计，包含不同粒径的布洛芬组合物和相对较低量的基质形成剂羟丙甲纤维素（HPMC）。标准级 HPMC（CR）与最近开发的可直接压级（DC2）进行了比较。研究结果表明，通过集成连续混合和直接压片，可以制备出具有所需质量属性的 ER 片剂。高混合速度和大粒径的布洛芬和 HPMC DC2 由于具有良好的粉末流动性，可获得最稳健的片剂质量（重量、含量、拉伸强度）。在低混合速度下，更难制备高质量的低剂量片剂。值得注意的是，对于含有 DC2 的组合物，与含有 CR 的组合物相比，HPMC DC2 的加工条件对药物释放有显著影响。与含有 CR 的组合物相比，含有 DC2 的组合物需要更长的加工时间和/或更快的混合速度才能实现稳健的释放。本工作证实了平衡工艺参数和材料性能以找到一致的产品质量的重要性。此外，自适应控制已被证明是控制连续制造系统的重要手段。
