Drug Dissolution Testing for the Sake of Testing?

Certainly, current practices of drug dissolution testing appear so. Let me explain …

For any analytical technique, there are two basic requirements which it must meet to be considered as an appropriate technique. (1) The technique must be able to provide relevant results and, (2) the technique must be able to provide reproducible results with acceptable variance. In terms of both requirements, dissolution testing would not meet the criteria of an appropriate analytical technique.

For a technique to provide relevant results, it must clearly be linked to a useful and measurable property of the sample. At present, dissolution testing is not linked to a property of the sample (drug product). Currently, it is quite often described as a tool for monitoring the “quality” of drug products, which is similar in concept to monitoring the “quality” of a person, a vague and undefined objective. Therefore, if the objective is vague and undefined then it is not possible to obtain relevant results. Thus, the outcome becomes testing for the sake of testing.

With regard to reproducibility, again, dissolution testing does not meet appropriate requirements. In response to the negative concerns often expressed in literature about the observed excessive variability of testing, suggestions are often made to tighten specifications and/or other controls, e.g. vessel diameter/curvature, removal of all sources of vibration, de-aeration, training of the analysts, and many more. The question would still remain, what should be the acceptable variations of the test and on what basis? Should the %RSD be 1% or 35% or in between and which value should be considered correct and acceptable? The only way to answer this is through multi-lab performance verification tests, such as USP conducts. Unfortunately, USP does not accept the results from its own studies which show lack of acceptable reproducibility of the test. Other regulatory bodies stopped using such a performance test as it does not SHOW acceptable reproducibility. However, there is continued acceptance of the results from the tests based on the assumption that the technique/test provides an acceptable level of reproducibility. It is not clear how, and on what basis that an acceptable level of reproducibility of the test/technique is assumed? Therefore, how would an analyst determine the reproducibility of the test and be able to differentiate it from the variability of his/her product or results. Thus, until and unless, the variability of the underlying test/technique is not known and established, dissolution testing will remain testing for the sake of testing.

It should, therefore, be kept in mind that if an analyst is expected to use dissolution testing, in particular using the paddle/basket apparatus, it is highly likely that the dissolution results will neither be relevant nor reproducible.

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