There is no argument that the drug dissolution characteristic of a product (tablet/capsule) is one of the most important and critical attributes. It is, and will remain, one of the critical parameters to evaluate for the development and evaluation of the products.

However, the issue is how should one measure the parameter (dissolution characteristics of a product) i.e. percent drug dissolved/released at times from a product? Obviously, one requires an apparatus/procedure to determine that. It is the most basic, and scientific, requirement for determining any characteristic/parameter the apparatuses/methods used must first be qualified/validated i.e. a priori shown to be fit for the purpose. However, none of the suggested/recommended apparatuses/methods have ever been shown as qualified and/or validated for dissolution testing. These are no different or better for dissolution testing than the use of a kitchen blender at a slower rpm.

It is, therefore, very important and critical to note that any results obtained using the suggested/recommended apparatuses/methods, in particular basket and paddle, have no scientific merit or use for any purpose, including QC, IVIVC, QbD, etc. One should be extremely cautious in drawing any conclusions based on data obtained using these unqualified and non-validated apparatuses.

It is important to note that de-aeration may impact dissolution results, just like testing at different temperatures or rpms can provide different results. Seeing different results does not mean much. These observations are pretty much irrelevant and useless for the purpose dissolution testing. The requirement of de-aeration is irrelevant, just like that of conducting dissolution tests at a higher or lower temperature would be.

Dissolution tests should always be conducted under relevant experimental conditions considering the objective of the testing. For an appropriate dissolution testing, the media temperature should be maintained at 37 ºC and the dissolved gasses levels should be equilibrated at this temperature. Results obtained otherwise would be considered scientifically invalid and useless for the purpose of evaluation of quality (e.g. QC) of products for human use.

No funny explanations or justifications, please!

It is a well-established fact that current dissolution apparatuses (paddle/basket) are flawed and cannot provide relevant and reproducible results. The flaw is because of poor hydrodynamics within a dissolution vessel i.e. product and medium do not interact appropriately and reproducibly resulting in cone formation, tablet/capsule positioning effects etc. Thus, tests provide highly variable and unpredictable results, which have been shown in many reported experimental studies.

Rather than addressing the issue or the flaw, unfortunately focus has been diverted in promoting that the reasons of such unpredictable behaviour are due to lack of control of de-aeration of dissolution medium and presence of vibration in and around the apparatuses.  It is important to note that there is no logical or experimental basis or evidence available in support of such a view. However, there are persistent discussions and promotions of such views.

It may be important to further note that this promoted view of the de-aeration or vibration aspect originated from frequent failures of calibration of apparatuses using USP prednisone tablets. The effect of de-aeration and vibration on actual products for human use is almost non-existent. The use of chemical calibration has already been considered unreliable because of the unpredictability of results or failure of perfectly working dissolution apparatuses. Their use is gradually diminishing, however, “slogans and chanting” of de-aeration and vibration continues.

Therefore, analysts should critically evaluate the promoted views on the topic as these are not scientifically valid claims.

The dissolution tests are conducted to evaluate drug release characteristics of products in the human GI tract, which is neither de-aerated nor vibration free. Therefore, conducting dissolution tests in a de-aerated medium and/or vibrating free environment should be considered as a physiologically irrelevant practice as well.

For appropriate dissolution testing, the medium should be equilibrated with dissolved gases at 37 ºC and stirred gently but thoroughly.

However, it is important to note that none of the currently suggested apparatuses and procedures can provide relevant and accurate dissolution results for any product.

The reason being NONE of the suggested and recommended apparatuses/procedures are qualified and/or validated for dissolution testing. Most, if not all, reported testing and results do not reflect dissolution characteristics of the products but rather the presumed ones, obtained by selecting product dependent experimental conditions. See link for further details (Drug dissolution testing: Limitations of current practices and requirements).

As all of the above mentioned guidances are dependent mostly on drug dissolution results, obviously, these documents cannot provide an intended and useful interpretation about the quality of pharmaceutical products in particular tablet and capsule.

A new or modified apparatus and/or procedure is required for appropriate uses/applications of the above mentioned documents. A modified dissolution tester with crescent-shape spindle, and a single set of experimental conditions may be used to address the flaws of the current practice providing improved product development and evaluation. Link for further details: A Simple and Unique Approach for Developing and Evaluating Products.