Drug dissolution tests are conducted to determine dissolution/release characteristics of a product. Therefore, one requires a pre-established set of experimental conditions (apparatus, rpm, medium volume or pH etc.) independent of the product so that the actual or true characteristics (i.e. dissolution) can be determined.

Current practices in particular using paddle and basket apparatuses, however, require that the analyst MUST first know, or anticipate, dissolution characteristics of the test product, and then ADJUST experimental conditions to achieve the desired or anticipated results. Selections or adjustments of such experimental conditions are then described or promoted, incorrectly, as dissolution method development practices. Almost every product comes with its own set of experimental conditions and expected dissolution results (commonly referred to as Tolerances). At present, one cannot know or determine the actual or true dissolution characteristics of the products. It is, therefore, very important and critical to note that current practices of dissolution testing are practically a complete waste of time and resources.

The suggestion of dissolution testing using the crescent-shaped spindle, along with a single set of experimental conditions (which are product independent as well) addresses the current issues and provides a simple, practical and scientifically valid approach for dissolution testing. For further detail please see these links (1, 2, 3).

It is important to note that drug dissolution tests are conducted for products (tablets/capsules) and not for drugs (APIs). Therefore, it is not accurate to use or develop drug-specific experimental conditions as commonly reported.

On the other hand, drug dissolution characteristics are mostly dependent on the formulation and manufacturing attributes of a product i.e. a dissolution test is conducted to evaluate the impact of formulation and manufacturing. Therefore, for determining dissolution characteristics of a product, the test must be independent of the formulation and manufacturing characteristics of the product under consideration. This means that one is required to use a pre-established dissolution test independent of the product under consideration. Developing a dissolution test for a product, which is being developed, and then using it to show its own dissolution characteristics, as currently done, is obviously a scientifically invalid practice.

Furthermore, it is to be noted that dissolution medium and other experimental conditions are linked to the physiology of the human GI tract, which remains constant, and also drug and product independent. Therefore, if one uses drug/product dependent experimental conditions, then this will make a dissolution test bio irrelevant and product evaluation pretty much useless, even for QC purposes. The following link may be of further help in this regard (link).

Recently I participated in a discussion on a LinkedIn forum (Quality by Design or QbD) explaining relevance and critical importance of drug dissolution testing for QbD, manufacturing of the products (tablet/capsules) and their evaluations.

Continuing on the topic, I believe a better organized explanation may be useful in clarifying issues related to the assessment of quality of pharmaceutical products. This article provides the explanation. It is important to note that the following discussion is restricted to tablet and capsule products only. Please click here for complete article

It is commonly accepted, and as described in one the FDA guidance documents (link), that “For highly water soluble (BCS classes 1 and 3) immediate release products using currently available excipients and manufacturing technology, an IVIVC may not be possible.” i.e. a relationship may not exist between in vitro dissolution and in vivo dissolution (as obtained from the bioavailability studies). Then, the obvious question is why should one use the dissolution test to evaluate such products, even for quality control purposes? The purpose of a QC test is to indicate potential deviation of in vivo drug release characteristics. However, if the assumption/view is that the relationship between in vitro and in vivo behaviour does not exist then what is the use of such a QC test, in particular for IR products with highly soluble drugs.  

The reality is that the relationship between in vitro and in vivo dissolution always exists, which forms the basis of conducting drug dissolution testing. However, the way drug dissolution tests are conducted at present, using commonly recommended apparatuses, in particular paddle and basket, do not measure the dissolution properties accurately and reproducibly which is reflected/considered as a lack of in vitro-in vivo relationship. In addition, dissolution studies were never intended to develop or establish IVIVC, but to use the relationship to predict plasma drug levels.

In this regard, if one uses a modified apparatus, such as with the crescent shape spindle, which provides appropriate product/medium interaction, then the dissolution tests can generate in vivo relevant results, as expected. For further details on conducting appropriate dissolution studies and in predicting blood levels please see the links (1, 2).

Before one uses a tester/method, it is mandatory, in particular in a GMP environment, that the validity of its use be established i.e. does the tester/method measure the expected characteristics of the product? In the case of a dissolution tester/method, one expects that it should measure the drug dissolution/release characteristics of a product and should be able to differentiate between products having different dissolution/release characteristics. In addition, a tester/method should not just measure and/or show such differences but these measurements and differences have to be relevant and useful. Please click here for complete article