What went wrong with the practice of drug dissolution testing?

It is important to note that the emphasis is on the “practice” and not the drug dissolution testing itself. A drug dissolution test is an important and extremely useful test and is required for the development and evaluation of pharmaceutical products, in particular tablets and capsules. However, how the test is conducted, referred here as the “practice,” is very different from dissolution testing itself. One should keep this difference in mind. 

There are numerous issues with the practice (or conducting a test). For example:

The test is to be done to determine drug dissolution characteristics of the product, but in practice it is done to establish experimental conditions to obtain pre-set (or preconceived) dissolution characteristics of the product. The analyst would never know the true drug dissolution characteristics of the product, thus its quality.

The most commonly used apparatuses, particularly paddle and basket, have never been validated to establish their suitability for drug release (or product) evaluation. These apparatuses usually do not even differentiate a slow-release product from a fast release product and vice versa. Thus, separate methods for these types of products are required. However, their use within the same product type is required to differentiate drug release based on manufacturing/formulation attributes.

Commonly, the practice is rationalized to monitor batch-to-batch consistency in product manufacturing. However, the consistency of the test (repeatability and reproducibility of the test itself) has never been established.

Often, tests are expected to be conducted using irrelevant experiment conditions, de-aeration in particular with a non-verifiable parameter or end point.

A product is expected to have more than one value (result) of the parameter (dissolution). Even USP performance verification tablets (USP) have two sets of dissolution results based on apparatuses used. The question is, what are the correct (true) dissolution characteristics of USP performance verification tablets?

The reason for these problems appears to be that for the past number of years, the focus has been to rationalize the use of paddle and basket apparatuses, which have been known to be flawed.

For appropriate testing, the focus must be on obtaining relevant and reproducible dissolution results of a product. The practice of adjusting experimental conditions to obtain certain desired or pre-conceived dissolution results should be discouraged.

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