Drug Dissolution Testing

 USP calendar shows an entry of a planed webinar to address the problems in the dissolution testing area. USP is requesting submission of questions so that issues and concerns may be addressed in this regard. The following are some suggested questions/concerns which USP may consider addressing during the webinar or later.

1. USP usually recommends the use of Paddle and Basket apparatuses for drug dissolution testing as a first choice. Are there any documented reasons (evidence) for these choices showing their superiority compared to other apparatuses? How have these apparatuses been validated as appropriate dissolution apparatuses to evaluate pharmaceutical products for human use?
2. Commonly, as a general practice, USP suggests experimental conditions for individual products (monographs) to establish their drug dissolution characteristics. This aspect is also described in more detail in the chapter <1092>. The practice requires that an analyst must know the product and its expected dissolution behaviors and then adjust the experimental conditions accordingly to achieve the expected characteristics. However, the objective of a dissolution test is to know or establish drug dissolution characteristics of a test product. How should this conflict be addressed?
3. Concerning the variability in dissolution results, how would an analyst determine (differentiate) whether the variability is related to the PVT (or a test product) or the apparatuses. Is information on the contribution to variability due to apparatuses available?
4. USP supplies prednisone performance verification tablets (PVT) which provides different dissolution results depending on the apparatus and experimental conditions employed. What would be the “true” (“actual”) dissolution characteristics of PVT as a product which may be used as “reference”?
5. Apparently, the prednisone performance verification tablets may be characterized as a fast-release product, but shows slower release type due to “cone” formation. The “cone” formation is the result of poor hydrodynamics and lack of product-medium interaction within dissolution vessels. Would it not be obvious that the products which will have similar characteristics like PVT would also be inaccurately characterized as slow release type when in fact they would be fast release type?
6. Why does the USP recommend that the dissolution medium be de-aerated?  What is the rationale for this suggestion, when apparently this suggestion would make the dissolution test irrelevant, as the physiological aspect does not require a de-aerated environment?
7. Pharmacopeial tests are often presented as tests for establishing batch-to-batch consistency in products’ quality, usually not as a bio-relevant test because the test often fails the IVIVC. If bio-relevancy or IVIVC is not the objective then any other test, such as disintegration test may be used for consistency checks. The reason the dissolution test was introduced to replace disintegration test was the lack of bio-relevancy of the latter. The majority of the pharmacopeial dissolution tests are not bio-relevant, so how should one justify a dissolution test over a disintegration test?