In a recent addition to USP 37 General Notices and Requirements (link), USP clearly describes that:
“Compliance with any of the [dissolution] tests does not assure bioequivalence or bioavailability”.
In reality, dissolution testing has been introduced as an alternative to bioequivalence (BE) or bioavailability (BA) evaluations based on the principle that the dissolution is one of the most critical parameters for the assessment of BE/BA. Therefore, drug dissolution tests must be conducted using physiologically relevant experimental conditions such as 37 ºC temperature, aqueous buffers within physiological pH range, moderate stirring, etc.
There has been a tremendous effort made in predicting BE and BA (e.g., predicting plasma drug concentration) using testers and methods commonly suggested in the compendia. Dissolution tests have been recommended for bio-waivers i.e., using them in lieu of BE/BA. In addition, it is a common practice and requirement that prior to a test becoming a compendial method, the product development step must use, or at least be tried, testers and methods to establish their relevance to BE/BA data. Eventually, the selected dissolution method would become the pharmacopeial test commonly known as QC-test or tool.
The underlying assumption for conducting the test remains that the test monitors potential in vivo dissolution, hence BE/BA. USP Chapter <1092> highlights and stresses that method development exercises should be relevant to in vivo performance describing “The procedure should be appropriately discriminating, capable of distinguishing significant changes in a composition or manufacturing process that might be expected to affect in vivo performance.” Numerous guidance documents, including those from the FDA, stress the dissolution and BE/BA link. Some of the examples to this effect from the FDA guidance’s are reported at the bottom of this post as an appendix.
Therefore, the recent addition to the USP, as noted above, does not make sense. Read the rest of this entry �