I read with interest the article authored by Tom Foster and Will Brown in the latest issue (February 2005) of Dissolution Technologies (http://www.dissolutiontech.com/DTresour/200502Articles/DT200502_A01.pdf), titled “ USP Dissolution Calibrators: Re-examination and Appraisal.”
Unfortunately, in describing the current status and future directions for dissolution testing and calibration in particular, the authors appear to have missed the recent literature on the subject. I hope this is not intentional. The latest reference cited in their article is from the year 2000. However, a quick search on Medline would have resulted in at least 10 more recent publications on the subject (for example, see below for some recent relevant references) from various authors and institutions. These latest publications, reflecting current scientific research and thinking, have shown that the cause of the problems in dissolution testing is not related to perturbation but to inherent deficiencies of the technique itself. Therefore, no amount of standardization of the current (USP 1 and 2) apparatuses and the calibrator tablets can control or minimize the issues and problems of the calibration or drug dissolution testing in general.
Furthermore, even if perturbations are controlled to “ ideal” levels, the technique is flawed to provide relevant dissolution results reflective of pharmaceutical and biological characteristics of the products.
Through this publication, I would like to request that USP should consider these recent observations described in the literature for the planning of future studies or evaluations.
Sincerely,
Saeed A. Qureshi, Ph.D.
Senior Research Scientist
Bureau of Pharmaceutical Sciences, TPD
Health Canada, Ottawa, Canada
Email: saeed_qureshi@hc-sc.gc.ca
Disclaimer: Views expressed here are for scientific discussion purposes only and may not be reflective of opinions and policies of my employer.
We appreciate Dr.Qureshi�s interest in our article and his observations about the increasing scientific attention being directed to the dissolution test. Unfortunately, we believe Dr.Qureshi misinterpreted the intent of our article. The authors did not intend to survey the entire field of dissolution science in the article originally published. Rather, the intent was to redirect focus to one aspect of dissolution testing, the calibrator tablet. We recognize that there is significant discussion among scientists about a number of elements of dissolution testing including acceptable processes for calibration of the instrumentation, and our article cited a number of publications regarding dissolution apparatus calibration. We did not intend the article as a comprehensive literature review. We recognize that there is a plethora of interesting studies that have been published in recent years on the dynamic environment represented by the dissolution test. There are equally a great number of published studies that examine the influence of hydrodynamics and other perturbation effects on dissolution performance and operational characteristics. We chose to cite publications that directly bear on the current calibrator reference standard material distributed by USP. Our desire in publication of the article was to bring focus to the calibrator as a means of assessing the dissolution apparatus performance summatively and not individual components; apparatus, operator and environment. We continue to espouse the value of dissolution testing and recognize that control of these factors is of paramount importance. Fortunately, most dosage forms are not subject to highly variable dissolution results. On those occasions where we do witness variability, caution should be exercised, and we are obligated to ensure that we redouble efforts to understand and minimize that variation. We look forward to further constructive commentary on dissolution testing and calibration of the testing systems.
Thomas Foster* and William Brown**
*Chair of the USP Expert Committee on Biopharmaceutics
** USP Staff Liaison, USP