Comparative in vitro dissolution studies may be useful in the documentation of equivalence between two multisource pharmaceutical products. Because of many limitations associated with the use of in vitro dissolution in the documentation of equivalence this guidelines recommends that its application for this purpose be kept to a minimum. Hence, in vitro dissolution testing as the sole documentation of equivalence is not applicable to drugs that fall within the criteria of the pharmaceutical products listed on p.117 from (a) to (e). This approach should also be reserved for rapidly dissolving drug products.1 When such multisource test and reference products, both dissolve with sufficient rapidity (e.g., >80% in 15 minutes), their in vivo equivalence may be presumed. Approval of multisource formulations using comparative in vitro dissolution studies should be based on generation of comparative dissolution profiles rather than single point dissolution tests, such as are described in various compendia. Multiple dissolution test conditions and physiologically relevant media are recommended.
1 Where a drug substance and drug product do not dissolve with sufficient rapidity, as noted above, in vitro dissolution methods might still be used to document equivalence using appropriately validated dissolution methodology to include a in vitro/in vivo correlation. Such methodology should derive from development and application of specifications and statistical methods to define nonequivalence. This development may require formulations with different in vivo performance characteristics. With such formulations, discriminating in vitro dissolution tests for use in equivalence studies may be developed. With these additional requirements, however, performance of a standard in vivo bioequivalence as described in section 7 may be preferable.