USP-NF Stimuli Article on the Use of Apex Vessels in Dissolution Testing

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In the current Pharmacopeial Forum, PF 47(6), a stimuli article entitled "The Case for Apex Vessels" was published.

The stimuli article can be viewed here. (Please note: a one-time registration is required to access the Pharmacopeial Forum.) The deadline for submitting comments is January 31, 2022.

Background

The dissolution test is a key test parameter routinely used for assessing the performance of solid and semi-solid dosage forms in both drug development and quality control.

The most commonly used apparatus for oral solid dosage forms is the paddle apparatus, often known as the USP Apparatus 2.

According to the authors of the stimuli article, it is intended to demonstrate the significant benefit of the apex vessels (previously known as PEAK vessels) relative to the standard vessel in overcoming coning for formulations that contain dense insoluble excipients.

Content of the Stimuli Article

In the stimuli article, after a detailed introduction to the topic, the following aspects are addressed:

• Methods and materials for interlaboratory study: To understand the impact of apex vessels produced by different dissolution bath manufacturers, an interlaboratory study was performed across 11 partners. All five major manufacturers (Agilent, Distek, Erweka, Hanson, Sotax) of dissolution baths and their associated apex vessels were represented. USP Prednisone Tablets RS (10 mg) were selected as the test article for the study and UV spectrophotometry was used as the analysis technique to determine the concentration of prednisone dissolved from the reference standard tablet.
• Methods and materials for CFD modeling: Computational fluid dynamics (CFD) was used to simulate the influence of small geometric differences in apex geometries of the five dissolution bath manufacturers on the hydrodynamics in the dissolution vessels. Six case studies were performed and the results are presented in the article.
• Results and discussion of interlaboratory study: The authors of the stimuli article conclude that "the practical impact of using different manufacturer systems and corresponding apex vessels was low, and therefore, any proposed specification is suitable to encompass the ranges observed across all five major manufacturers."
• Results and discussion of CFD study: In this subchapter of the article, the simulated hydrodynamics in an apex vessel and a comparison of the simulated shear rate distributions across the different vessel geometries for the region around the paddle and below are presented.
• Proposed specification of apex vessel: A specification (apex dimensions, apex height, apex cone angle, apex centering) is proposed.
• Qualification of apex vessel: The authors propose "that any dissolution apparatus that will be used with apex vessels will first be qualified according to the company protocols regarding enhanced mechanical and/or PVT qualification. Subsequent to the completion of the qualification with standard vessels, these will be replaced with validated apex vessels."
• Conclusion: It is the authors’ intent by publishing the article "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 <1092> and ultimately inclusion into the USP chapter Dissolution <711> and other harmonized pharmacopoeia as an alternative vessel to the standard 1-L vessel to be used when scientifically justified.