Stimuli to the Revision Process: The Case for Apex Stimuli articles do not necessarily reflect the policies of the USPC or the USP Council of Experts

摘要

Apex vessels (previously known as PEAK vessels) are an important element of the dissolution scientist's toolbox and are frequently used in pharmaceutical drug product development settings. However, their use in development has not translated widely into use in the final approved quality control (QC) method. This Stimuli article aims to demonstrate the significant benefit of the apex vessel relative to the standard vessel in overcoming coning for formulations that contain dense insoluble excipients. Industrial case studies outline the benefits obtained by the apex vessel such as improved clinical relevance, more robust and discriminatory methods, and streamlined in vitro bridging strategies. Furthermore, to understand the impact of apex vessels produced by different dissolution bath manufacturers, an interlaboratory study was performed across 11 partners, which demonstrated minimal differences in dissolution performance between partners when a controlled protocol was executed. This was supplemented by a comparison between the different manufacturer designs using a computational fluid dynamic model, which showed no significant differences between manufacturers. This led to a manufacturer proposed specification for an apex vessel alongside a qualification procedure for the use of the vessels. It is the authors' intent by publishing this article that it will stimulate discussion leading to greater acceptance of the apex vessel such that it will be considered for a more prominent inclusion in future pharmacopeial chapters such as the US Pharmacopeia (USP) chapter The Dissolution Procedure: Development And Validation and ultimately inclusion into the USP chapter Dissolution and other harmonized pharmacopoeia as an alternative vessel to the standard 1-L vessel to be used when scientifically justified.