Heinrich Heine University, Institute of Pharmaceutics and Biopharmaceutics, Universitaetsstr. 1, 40225 Duesseldorf, Germany; ONO Pharmaceutical Co., Ltd., CMC & Production HQs, Pharmaceutical Product Development & Management, Pharmaceutical Product Development, Non-Sterile Product, 15-26 Kamiji 1-Chome Higashinari-ku, 537-0003 Osaka, Japan.
Heinrich Heine University, Institute of Pharmaceutics and Biopharmaceutics, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Int J Pharm. 2020 Apr 15;579:119139. doi: 10.1016/j.ijpharm.2020.119139. Epub 2020 Feb 13.
This study aimed to transfer a high shear granulation (HSG) process to a twin-screw granulation (TSG) process while maintaining equivalent dissolution profiles. Ibuprofen (IBP) was used as poorly soluble model drug. Granules were obtained by HSG or TSG according to a full factorial design. The liquid-to-solid ratio and wet massing time (HSG) or powder throughput (TSG) were selected as factors. The granules were compressed to tablets with immediate release and a drug load of 50% (w/w). Quality attributes (QAs) of the granules, especially the granule strength (GS), and the resulting tablets were evaluated. The effect of process parameters on the QAs was statistically analyzed. The comparison of HSG tablets with TSG tablets revealed that TSG tablets showed higher tensile strength and lower ejection force than HSG tablets. The dissolution profiles of the tablets in different pH media were also evaluated. Equivalent dissolution profiles in all four media (e.g., f values ≥ 54 in pH5.5) were obtained by adjusting process parameters. It was concluded that the GS was the most important QA for dissolution.
本研究旨在将高剪切制粒（HSG）工艺转化为双螺杆制粒（TSG）工艺，同时保持等效的溶解曲线。布洛芬（IBP）被用作难溶性模型药物。根据完全析因设计，通过 HSG 或 TSG 获得颗粒。液体与固体的比例和湿混时间（HSG）或粉末吞吐量（TSG）被选为因素。将颗粒压缩成片剂，具有速释和 50%（w/w）的载药量。评估了颗粒的质量属性（QAs），特别是颗粒强度（GS）和由此产生的片剂。使用统计学方法分析了工艺参数对 QAs 的影响。HSG 片剂与 TSG 片剂的比较表明，TSG 片剂的拉伸强度高于 HSG 片剂，而推出力低于 HSG 片剂。还评估了不同 pH 介质中片剂的溶解曲线。通过调整工艺参数，在所有四种介质（例如，pH5.5 时 f 值≥54）中均获得了等效的溶解曲线。结论是，GS 是溶解最重要的 QA。
