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.
Keywords: Bioequivalence; Biowaiver; Coning; Dissolution test, Tablet; Sinker.
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