USP is seeking comments on a draft of the revised “General Chapter <1092> The Dissolution Procedure: Development and Validation” (link). Also provided is a Stimuli article: “Revision of <1092> The Dissolution Procedure: Development and Validation” (link), which is to be published along with the proposed General Chapter providing the background information for the suggested revisions.
The following provides some comments for the consideration of the USP:
(1) In general, the chapter appears poorly written lacking focus and coherence of thoughts.
(2) The claims made in the article, for method development or validation, are not only vaguely described but are also scientifically invalid. For example:
- The suggested apparatuses, in particular paddle/basket, are known to be flawed (lack reproducibility and relevancy) and have never been validated. Therefore, developing or validating a method using such apparatuses would not be possible.
- For validating a method, one requires a reference such as a product, parameter value (e.g. dissolution results) and/or experimental conditions established independently. As such a reference is not available at present, thus the dissolution methods cannot be developed in particular for setting regulatory/pharmacopeial standards such as for USP.
- The suggested approach of method development appears to be a vague narration of selecting experimental conditions to obtain certain pre-defined or pre-conceived dissolution characteristics of a product, not for determining the true characteristics of a product. It is important to note that the choice of the experimental conditions should be linked to the GI tract environment and not the product. As the physiological conditions (or experimental conditions) remain constant or independent of the drug/product, one should not be able to vary experimental conditions. The suggestions in the chapter concerning selecting product-dependent experimental conditions are scientifically invalid for the purpose.
- In general, if given a blinded product sample, which is a normal and common analytical practice, no matter how thoroughly or attentively one would follow the suggestions provided in the chapter it would not be possible to determine relevant and/or true dissolution characteristics of any product.
USP should consider addressing the above mentioned deficiencies before finalizing the chapter.
