Photo-Acoustics Research Laboratory, Department of Mechanical and Aeronautical Engineering, Clarkson University, Potsdam, NY 13699-5725, USA.
University of Maryland, School of Pharmacy, Baltimore, MD 21201, USA.
Int J Pharm. 2018 Dec 20;553(1-2):338-348. doi: 10.1016/j.ijpharm.2018.10.052. Epub 2018 Oct 24.
Capping is a common mechanical defect in tablet manufacturing, exhibited during or after the compression process. Predicting tablet capping in terms of process variables (e.g. compaction pressure and speed) and formulation properties is essential in pharmaceutical industry. In current work, a non-destructive contact ultrasonic approach for detecting capping risk in the pharmaceutical compacts prepared under various compression forces and speeds is presented. It is shown that the extracted mechanical properties can be used as early indicators for invisible capping (prior to visible damage). Based on the analysis of X-ray cross-section images and a large set of waveform data, it is demonstrated that the mechanical properties and acoustic wave propagation characteristics is significantly modulated by the tablet's internal cracks and capping at higher compaction speeds and pressures. In addition, the experimentally extracted properties were correlated to the directly-measured porosity and tensile strength of compacts of Pearlitol, Anhydrous Mannitol and LubriTose Mannitol, produced at two compaction speeds and at three pressure levels. The effect compaction speed and pressure on the porosity and tensile strength of the resulting compacts is quantified, and related to the compact acoustic characteristics and mechanical properties. The detailed experimental approach and reported wave propagation data could find key applications in determining the bounds of manufacturing design spaces in the development phase, predicting capping during (continuous) tablet manufacturing, as well as online monitoring of tablet mechanical integrity and reducing batch-to-batch end-product quality variations.
顶裂是片剂生产中常见的机械缺陷,出现在压缩过程中或之后。预测片剂顶裂与工艺变量(例如压缩压力和速度)和配方特性有关,这在制药行业中至关重要。在当前的工作中,提出了一种非破坏性接触超声方法,用于检测在各种压缩力和速度下制备的药物片剂中的顶裂风险。结果表明,提取的力学性能可作为隐形顶裂(在可见损伤之前)的早期指标。基于 X 射线截面图像和大量波形数据的分析,证明了片剂内部裂缝和顶裂会显著调制片剂的力学性能和声波传播特性,尤其是在较高的压缩速度和压力下。此外,还将实验提取的性能与直接测量的压坯孔隙率和拉伸强度相关联,这些压坯是由两种压缩速度和三种压力水平下生产的 Pearlitol、无水甘露醇和 LubriTose 甘露醇制成的。定量研究了压缩速度和压力对所得压坯的孔隙率和拉伸强度的影响,并将其与压坯的声学特性和力学性能联系起来。详细的实验方法和报告的波传播数据可以在开发阶段确定制造设计空间的边界、预测(连续)片剂制造过程中的顶裂以及在线监测片剂机械完整性和减少批与批之间的最终产品质量变化方面找到关键应用。