Investigation of Dissolution Performance of Hard Gelatin Capsule Products Using Various Sinkers

Abstract

Dissolution testing is a commonly used tool for the quality control of various dosage forms. For this purpose, consistent test conditions are necessary to obtain reproducible test results. Typical issues that can affect the dissolution performance of tested capsule formulations are floating and coning. Recently, the International Conference on Harmonisation (ICH) guideline recommended the use of sinkers to prevent coning, although no accompanying data to support the recommendation has been published in the open literature to date. Therefore, we initiated studies designed to address the following key questions. A) Do all sinkers prevent flotation of the dosage form? B) Does using sinkers consistently increase the dissolution rate? C) Do sinkers consistently decrease coning? Three commercially available hard capsule drug products were studied: acetaminophen, fluconazole, and ketoprofen. Dissolution was performed without a sinker and with four commercially available sinkers (CLIPS, CAPLOTH, CAPWAST, and JP). Analysis of the results revealed that, although three of the four sinkers were able to adequately address flotation problems, in many cases their use led to artifactual increases or decreases in the dissolution of the capsules. Further, sinkers do not seem to be generally useful for addressing coning issues. Instead, an increase in the stirring speed or use of peak vessels should be considered.