It is commonly accepted, and as described in one of 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. So then, the obvious question is why one should use the dissolution test to evaluate such products, even for quality control purposes? The purpose of a QC test is to indicate the potential deviation of in vivo drug release characteristics. However, if the assumption/view is that the relationship between in vitro and in vivo behavior does not exist, what is the use of such a QC test, particularly 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 for drug dissolution testing. However, the way drug dissolution tests are conducted at present, using commonly recommended apparatuses, particularly paddle and basket, does 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).