Univ. Bordeaux, CNRS, Arts et Metiers Institute of Technology, Bordeaux INP, INRAE, I2M Bordeaux, F-33400 Talence, France.
Research and Development Division, F. Hoffmann-La Roche AG, Basel, Switzerland.
Int J Pharm. 2022 Jun 10;621:121818. doi: 10.1016/j.ijpharm.2022.121818. Epub 2022 May 12.
Capping is a common defect that can occur during the manufacturing of pharmaceutical tablets. Several studies showed that decreasing the unloading speed of the manufacturing cycle plays a role in the occurrence of such defects. Following this idea, we study in this work the influence of the unloading step on capping using a compaction simulator. Measuring the die wall pressure made it possible to detect precisely that tablets capped just after the unloading (some milliseconds only). To evaluate the impact of the unloading speed on capping, we developed a two-step unloading phase controlled by three manufacturing parameters. It was possible to mitigate capping by decreasing the speed at which the contact between the punches and the tablet was lost. Capping seemed due to dynamical effects related to the release of the axial pressure. The modification of the unloading step to mitigate capping led to significant changes in tablet density but no clear trends were found for the residual die-wall pressure and tablet strength. This work made it possible to improve the understanding of capping. Moreover, the two-step unloading cycle gave a new idea for possible modifications that could be done on rotary presses in order to mitigate capping.
顶裂是片剂生产过程中的一种常见缺陷。有几项研究表明,降低生产周期的卸模速度有助于减少此类缺陷的发生。基于这一思路,我们在这项工作中使用压片机模拟装置研究了卸模步骤对顶裂的影响。通过测量模壁压力,我们可以精确地检测到片剂在卸模后几毫秒才出现顶裂。为了评估卸模速度对顶裂的影响,我们开发了一种由三个制造参数控制的两步卸模阶段。通过降低冲头与片剂之间失去接触的速度,可以减轻顶裂。顶裂似乎是由于与轴向压力释放相关的动力学效应引起的。通过修改卸模步骤来减轻顶裂,导致片剂密度发生显著变化,但残余模壁压力和片剂强度没有明显趋势。这项工作有助于提高对顶裂的理解。此外,两步卸模循环为可能在旋转压片机上进行的改进提供了新的思路,以减轻顶裂。