Limitations of drug dissolution testing using Apparatus 1 and 2

In a recent publication, USP describes the dissolution procedure as,

The procedure can function both as a quality control tool and, under specified circumstances, as a predictor of the dosage form’s performance in vivo.

One may interpret this as an indication of very weak support for the continuation of the procedure, at least in its current format.

Stating that the procedure could predict the product’s in vivo performance under certain specified circumstances is a clear deviation from the commonly accepted understanding. Furthermore, the only reason a dissolution test was introduced was to replace a disintegration test which was considered a poor predictor of in vivo performance of the products. Therefore, now as per the publication, the current dissolution procedure appears to have the same limitation as that of the disintegration test, which obviously has limited use.

Further, if the procedure is to work in some cases, one would require some form of guidance in determining how these specified circumstances are to be determined or established.

On the other hand, describing the procedure as a quality control tool may also become redundant without in vivo relevance. In general, it is accepted that if a dissolution test, as a quality control tool, shows unexpected drug release, it would reflect potential unexpected in vivo drug release of the drug, leading to concerns about the quality of the product. However, if the in vitro and in vivo link is severed or weak, what would be the rationale for using a dissolution procedure as a quality control tool?

The publication appears to have added serious confusion regarding the usefulness of the PVT procedure and the current practices of dissolution testing.

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