December 10, 2006
Sir,
I would like to share my views on the concept of “discriminating dissolution method” in light of the recent article titled “Developing Discriminatory Drug Dissolution Tests and Profiles: Some Thoughts for Consideration on the Concept and Its Interpretation, ” by Dr. Saeed A. Qureshi.
Discrimination, in the dissolution world, refers to the ability of a dissolution test method to identify the differences in formulation changes (manufacturing and compositional variations).When a dissolution test method is finalised for a bio-successful batch/product, it is generally expected that the test method should have some ability to distinguish other batches/products that vary from the biosuccessful batches. But the fact is that these batches may or may not be bioequivalent to the reference product. One cannot perform in vivo studies on all batches to establish method discrimination; rather, one tries to develop a method that can sufficiently differentiate between a biosuccessful batch and other batches (by intentionally varying manufacturing variables) and, thus, it is expected that any future batch with different manufacturing or compositional variations is likely to be invalidated by the test procedure. This forms basis for the discriminating ability of a dissolution method.
But Dr.Quereshi, in his article, has established an impression that the discrimination is used as the ability of the technique to match in vitro and in vivo dissolution results.The discussion about the relevancy of the technique is beyond the scope of this letter.
The author has emphasized the need for product-independent test methods on the grounds that the in vivo environment is same for all products.However, the author has missed the point that all formulations need not react in a similar way for the same environment. In vitro dissolution is, in fact, to evaluate these differences only.
Yours
RC REDDY.
rc_12321@yahoo.com
I appreciate the comments from RC Reddy on my recent article as well as interest in our work. Indeed, the objective of the referred publication was to highlight the shortcomings of current practices in conducting dissolution testing and interpreting the obtained results. Although I agree with RC Reddy’s view that common practices in dissolution testing are to observe differences in manufacturing and/or formulation attributes of the test product, in reality, by doing so, one does not gain any benefit from such testing. Although not mentioned, it is generally implied that observed differences in dissolution results corresponding to manufacturing and/or formulation attributes may indicate substandard physiological product characteristics.Therefore, dissolution behaviour has always been linked, explicit or otherwise, to the product’s physiological characteristics. This is precisely the objective of the referred publication, to highlight and emphasise this link, that conducting dissolution testing without a reference to a physiological link may not be accurate.
Furthermore, for conducting proper comparative dissolution testing (within a product category or between types, such as IR vs ER), the test methodology has to be the same, (i.e., product independent), otherwise comparative testing would not be valid. By keeping the methodology and testing environment the same, only then would one be able to accurately evaluate and differentiate how products would react to the testing environment.
Saeed A. Qureshi, Ph.D.
Senior Research Scientist
Bureau of Pharmaceutical Sciences
TPD, Health Canada
Ottawa, Canada
Disclaimer:Views expressed here are for scientific discussion purposes only and may not be reflective of opinions and policies of my employer, Health Canada.