Development of a Discriminating Dissolution Method Using Apex Vessels for Enzastaurin Tablets

Introduction: This study aims to develop a discriminating dissolution method for 125-mg enzastaurin tablets using a United States Pharmacopeia (USP) apparatus 2 (paddle) with apex vessels.Methods: The release rate of enzastaurin tablets was studied using conventional USP vessels and apex vessels.Various dissolution operational parameters were evaluated including rotation speed, media composition, and medium volume.The dissolution method using apex vessels was developed and its discriminating power was evaluated by making deliberate changes in the drug product formulation and manufacturing process.Results: Dissolution of the enzastaurin tablets using USP vessels lacked discrimination power at the standard 75 rpm paddle rotation speed; further studies with different rotation speeds and medium volumes also lacked discrimination power.When the rotation speed was below 75 rpm, the drug release rate was slow and incomplete due to a coning effect.When apex vessels were used, the dissolution method was able to discriminate between formulation and manufacturing process changes.Conclusion: A discriminating dissolution method for enzastaurin tablets was developed using USP dissolution apparatus 2 with apex vessels at 35 rpm and 500 mL medium volume.The use of apex vessels reduced the coning effect, and this method was able to detect drug product formulation and process changes, while the method using conventional USP dissolution vessels was found to be non-discriminating.