If one cannot determine dissolution characteristics of a product then how would one be able to establish its quality or bio-relevance? A serious flaw of current practices!

To establish the quality of a product or bio-relevancy of dissolution results, obviously, one first has to determine the dissolution characteristics of the product. To determine relevant dissolution results, one is required to have an agreeable or validated dissolution method (tester and experimental conditions).  The difficulty is that, at present, one does not have an agreeable or validated dissolution method or tester. Thus one cannot determine dissolution characteristics of a, or any, product as a result of its quality and/or bio-relevancy.

At present, people are trying to develop a dissolution method for the test product. However, it is impossible to develop a method using a product that is under development or evaluation. Therefore, a (dissolution) method can only be developed using a product of known or agreeable dissolution characteristics (i.e., a reference product).

It is important to note that the current practices of method development for dissolution testing are not at all method development practices as one does not have a reference product with known dissolution characteristics. On the other hand, one cannot determine the dissolution characteristics of any product, as one does not have a validated dissolution method or tester. Therefore, it is not possible to evaluate the quality of the product and/or the relevancy of dissolution results to in vivo results.

The current practice of drug dissolution testing often implies the development of dissolution methods rather than determining dissolution characteristics of the test product. There are hundreds, if not thousands, of dissolution methods available in the literature, not only drug/product specific but also application-specific (QC, bio-relevant, IVIVC, etc.). The important point is that there is a serious (flawed) mindset as people develop dissolution methods by assuming or expecting, a priori, dissolution characteristics of the product rather than using a dissolution method to determine the product’s dissolution characteristics. Therefore, it is very important to note that using the current dissolution testing practices or thinking one never determines dissolution characteristics.

Another way of saying the same is that the development of a dissolution method and the use/application of a dissolution method for the assessment of the quality of a product or its bio-relevancy are mutually exclusive exercises. They cannot be done together. Suppose one is using a dissolution method to develop a product or evaluate its characteristics (most common use of dissolution testing). In that case, one cannot develop a dissolution method at the same time. The validated dissolution method must be available a priori and independent of the product under consideration. People who are involved in such exercises (product development and evaluation) should pay attention to the current scientifically invalid practices.

For further discussion on the topic and potential solutions to such difficulties, the following link may help.

(1)    Why are current practices of dissolution testing so confusing, frustrating, and complex? Because they are not based on scientific principles but rituals! (link)

(2)    Assessing drug dissolution characteristics using product-dependent methods is simply unscientific and invalid practice. (link)

(3)    Dissolution method development: Perhaps the most wasteful of all the current practices! (link)

(4)    Worth repeating it: Drug and/or product-dependent dissolution tests are scientifically invalid. They do not provide dissolution characteristics of products even for QC purposes. (link)

(5)    A simple approach to assess the validity of a dissolution tester/method (link)

(6)    Drug dissolution testing: Limitations of current practices and requirements (link)

(7)    Presently, only the use of the crescent shape spindle provides true dissolution characteristics of a product (link)

(8)    The science of drug dissolution testing: Testers or apparatuses, experimental conditions and interpretation of results – A systematic approach for learning (link)

(9)    Selecting a Dissolution Apparatus – Some Practical Considerations (link)

(10)  A Simple and Unique Approach for Developing and Evaluating Products (link)

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