Current practices of drug dissolution testing are not aligned with expectations or requirements.

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).

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