Simplification to a “universal” dissolution test

It is often considered to be highly unlikely, if not impossible, to have a universal dissolution test. Let us explore whether this is a myth or reality?

Most commonly used dissolution methods are those described in the USP monographs (500+) and FDA database (500+). Examined closely, one observes that the majority (~76%) of the tests employ a paddle apparatus at 50 rpm (see US FDA database). Evaluation of USP monographs most likely would also lead to the same conclusion.

As for the dissolution medium, majority (~60%) of the tests employs water or aqueous based buffers in the pH range of 5 to 7.

If one considers the two previous practices together, it appears that we already have a “sort of” universal test which is paddle at 50 rpm using medium having pH in the range 5 to 7, which may be water or a buffer. Furthermore, it should also be noted that these conditions are commonly applied for both IR and ER products. Then why do not we use these “universal” test conditions, and have so many (hundreds) sets of dissolution experimental conditions?

One of the most common deficiencies in using this set of experimental conditions is that the results obtained are often slower and highly variable than expected. This is a normal and expected behavior of paddle spindle as the spindle rotation speed of at 50 rpm does not provide efficient product/medium interaction (figure) and movement of solvent (medium) upwards. The issue in this lies with one of the suggestions to address this limitation, which is to increase the rpm. Therefore a significant number (~18%) of tests are conducted at higher rpm of 75-100. However, there are no established criteria available to select an appropriate rpm, other than to obtain the expected dissolution characteristics of the product. Therefore, an analyst has to select a higher spindle rotation speed (rpm) arbitrarily. Interestingly, this practice of selecting the higher rpm is contrary to the popular belief/recommendation that a desirable characteristic of a dissolution test is that it should be discriminating. It is a well established fact that at a higher rpm the test becomes less discriminating. Therefore, the suggestion of changing the rpm lack scientific merit as well as adds randomness to the test by selecting an arbitrary rpm or experimental condition.

On the other hand, regarding the other variables of pH and nature of the buffer used for the testing, it is very difficult to explain. At best, it can be said that choices are random and arbitrary as well, again the criteria of selecting these variables are to achieve expected dissolution behavior, perhaps by adjusting the solubility/wetting characteristics of the product. This choice is often made by trial and error approach and without a clear and defined objective.

In short, it can be said that the commonly suggested or popular experimental conditions are paddle rotating at 50 rpm with a medium (water or buffer) having pH 5-7. However, when one does not achieve expected dissolution results, which is often the case, then analysts are free to select a different condition. This practice creates randomness and arbitrariness in the testing, which is currently reflected in the availability of such a large number of dissolution test conditions.

On the other hand, if one would use a different stirrer, crescent-shaped spindle is one such example, which provides improved stirring and mixing then issues using paddle would be addressed. Indeed, it has been demonstrated with the use of crescent shaped spindle, even at lower rpm of 25, many products can be analyzed using a single set of test conditions. The suggested “universal” set of experimental conditions is rpm=25 with water as a medium.

In conclusion, a universal dissolution test approach is already being used/suggested, however, it success has not be materialized because of the poor mixing/stirring aspect of the spindle. If this flaw is addressed, such as with the use of crescent-shaped spindle, then development of a universal dissolution test appears a genuine possibility.

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