A common query with regard to a dissolution test is how one should conduct the test for a drug. Further, in response to such queries, different suggestions are made for choosing the apparatus, rpm, medium etc. However, unfortunately, such queries and the responses lack scientific merit and logical thinking. The reason is that a dissolution test is conducted for a product and not for a drug (active ingredient). That is why pharmacopeial monographs, in particular USP, do not have dissolution tests under drugs (active ingredients) but products.

Therefore, one can only suggest a testing procedure for products and not for drugs. Further, a testing procedure is not, or should not, be linked to a product, because testing is done to evaluate product. Therefore, the procedure must be product independent. The question then becomes how one should set up the experimental conditions. The answer is that the dissolution testing conditions should be reflective of the GI tract environment, in particular intestinal. As the GI tract environment does not change from product to product, the testing procedure therefore should be fixed as well.

 A common testing environment may be based on water maintained at 37 °C, with some solubiliser to dissolve low aqueous solubility drugs, and a simple stirring mechanism which should provide efficient/thorough product-medium interaction.  Hope this suggestion will help in answering the common and frequent queries.

In a recent publication, USP describes prednisone based performance verification test (PVT) as,

“Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing)”.

It appears that that the use of PVT has been reduced to establishing the appropriateness of vessels and degassing of the medium rather than a performance evaluation test for the apparatuses or procedure as it is supposed to. Even claims for sensitivities of the two suggested parameters may be of questionable merit. Because; Continue reading →

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 be a predictor of in vivo performance of the product under certain specified circumstances, is a clear deviation from the commonly accepted understanding. 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, then what would be the rationale of 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.