Biopharmaceutics, Pharmaceutical R&D, CMC & Production, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan; Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Int J Pharm. 2024 Jun 25;659:124236. doi: 10.1016/j.ijpharm.2024.124236. Epub 2024 May 18.
The objective of this research is to explore the impact of sinkers on the dissolution rate of tablets exhibiting coning in paddle dissolution tests. The ICH M9 guideline refers to the use of sinkers to mitigate coning issues. However, the effectiveness of sinkers on coning phenomena has not been comprehensively investigated. Therefore, this study evaluated whether applying sinkers of different shapes could alleviate coning problems. The dissolution profiles of amlodipine tablet formulations which had been clinically demonstrated to be bioequivalent were assessed in a USP2 Apparatus with and without sinkers. Moreover, the effects of artificially induced coning formed by adding cellulose particles of various sizes on dissolution profiles, and the impacts of sinkers on the dissolution delay caused by the cellulose particles were investigated. Our study suggested that the CLIPS sinker was effective in obtaining in vivo relevant dissolution profiles by facilitating the dispersion of coning. The effect of sinkers varied depending on their shapes and the characteristics of the particles that constituted the coning. These findings enhance our understanding of the effectiveness of sinkers in addressing coning issues and aid in predicting the in vivo dissolution performance of tablet formulations that exhibit coning during dissolution testing.
本研究旨在探讨在桨法溶出试验中出现的片剂“楔入”现象对片剂溶出速率的影响。ICH M9 指南中提到使用沉降篮来减轻“楔入”问题。然而，沉降篮对“楔入”现象的有效性尚未得到全面研究。因此，本研究评估了使用不同形状的沉降篮是否可以缓解“楔入”问题。评估了在 USP2 仪器中添加和不添加沉降篮时，已经临床证明生物等效的氨氯地平片剂配方的溶出曲线。此外，还研究了通过添加不同大小的纤维素颗粒人为诱导“楔入”对溶出曲线的影响，以及沉降篮对纤维素颗粒引起的溶出延迟的影响。我们的研究表明，CLIPS 沉降篮通过促进“楔入”的分散，有效地获得了与体内相关的溶出曲线。沉降篮的效果取决于它们的形状和构成“楔入”的颗粒的特性。这些发现增强了我们对沉降篮解决“楔入”问题的有效性的理解，并有助于预测在溶出试验中出现“楔入”现象的片剂配方的体内溶出性能。
