Monthly Archives: April 2013
Note that no one can determine, or has determined, dissolution characteristics of any product using the currently suggested apparatuses and/or methods. It has all been an illusion!
The purpose of a dissolution test is to determine or establish drug dissolution or release characteristics of a product, in particular tablet or capsule. To determine dissolution characteristics, or any other characteristic in general, one would require a method and/or tester or apparatus. Prior to its use, it must be established that the method/tester is capable of providing an expected outcome, i.e. in this case the method/tester is capable of providing dissolution characteristics of a (tablet/capsule) product. In other words, the dissolution method/tester should be qualified and validated.
Unfortunately, at present, suggested and commonly used dissolution testers have never been shown as qualified and validated dissolution testers. Therefore, reported results, and by extension conclusions drawn from these results, are of limited or no relevance or use. It is all an illusionary science and interpretation of data/results.
The crescent shape spindle has been proposed to address this present-day difficulty. The use of the spindle provides an ability to test products using a common, simple testing and product-independent approach.
Comments on a recent article
I read a recent article published in the American Pharmaceutical Review titled “A Rational Approach to Development and Validation of Dissolution Methods” by G.P. Martin. In the article author suggested approaches one may take in developing drug dissolution testing methods.
It is unfortunate that the author ignored the current views and literature highlighting flaws of current practices of drug dissolution testing. Not only are the scientific approaches described in the articles are weak, more appropriately inaccurate, but the logical thinking would also not support the arguments presented. For example, it is stated that:
Why are current practices of dissolution testing so confusing, frustrating and complex? Because they are not based on scientific principles but on rituals!
Scientific rationales/requirements dictate that:
(1) A dissolution test should be conducted to reflect in vivo dissolution characteristics of a product (tablet/capsule). However, if and when results appear to match/associate with in vivo results (which are rare) then the test will be considered successful, otherwise, the failed tests will still be considered acceptable and used for assessing the quality of future batches.
(2) The failed or irrelevant dissolution methods should not be acceptable but are considered “fit for use” for the evaluation of quality of product for human use. Almost all tests at present, in particular pharmacopeial, are of this type. Continue reading
Assessing drug dissolution characteristics using product dependent methods is simply unscientific and invalid practice.
Evaluating dissolution characteristics of different products (e.g. IR and ER) using different methods is like measuring temperatures of a drink and meal/bread using two different scales with a justification that they have different contents and/or are prepared differently. Bizarre!
It is hard to believe that in this day of age, we are to follow such unscientific, illogical and invalid reasoning and practices.
If two different temperature scales (or thermometer scales) are to be used to monitor temperatures of drink and meal/bread, then how will one establish which one is hotter/colder than the other?
Similarly, if dissolution/release characteristics of different products are to be measured using two different scales (in this case methods, in particular product specific methods), then how will one know which one is of faster release and which one is slower release type?
In conclusion, using the current practices of dissolution testing one never determines the dissolution/release characteristics of any product. For appropriate testing, it is essential to have single and product independent tester and/or method.
Predicting plasma drug levels does not require an IVIVC development. In fact IVIVC cannot be used for such predictions at all, as explained with an example from literature for gliclazide ER products
It is often suggested that conducting IVIVC studies, i.e. developing a relationship between in vitro (dissolution) and in vivo (plasma drug level), are necessary for developing dissolution tests capable of reflecting or predicting plasma drug levels. Unfortunately, this is not a correct view, as explained below:
