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.

(3)    The apparatuses/methods must be qualified and validated for their intended purpose. However, currently recommended apparatuses have never been validated or qualified for dissolution testing purposes. On the other hand, these apparatuses are the only ones which are expected to be used. If new or different apparatuses are to be used then those are expected to provide comparable/similar results obtained using current apparatuses. That is, new apparatuses should also provide as irrelevant results as the current ones.

(4)    There should be a common product independent method/approach available to determine dissolution characteristics of a product. However, current practices require development and the use of product dependent methods, which obviously cannot provide dissolution characteristics of the product. There are hundreds, if not thousands, of dissolution methods available to use, in particular from pharmacopeias and standard setting authorities. However, in reality all these methods are not methods at all, but sets of instructions to follow to obtain desired or expected dissolution results of products.

(5)    Both IR and ER type products are to be tested using the same set of experimental conditions, as the experimental conditions represent/simulate the human GI tract environment which remains the same or constant. However, IR and ER products are expected to be tested using different in vitro experimental conditions even when comparisons are to be made with the in vivo results.

(6)    Some form of guidance or standards should be available to link in vitro dissolution results to the in vivo (bioavailability) outcomes. However, there are no such standards or criteria available. Often, in vitro and in vivo results are compared using eye-balling technique (commonly referred to as rank-order match or comparison). Such qualitative (eye-balling) approach should be considered invalid, as the data obtained and presented from two sources are in different units and scales. The in vitro dissolution data is often presented in percentage units using a linear scale while in vivo results are in concentration units (e.g. ng/mL) and exponential base.

(7)    The relationship between dissolution (in vitro or in vivo) and absorption/bioavailability should be used to predict plasma drug levels, the only objective for conducting drug dissolution testing. However, often requirements are imposed for developing a relationship as a mathematical model (equation) which provides no possibility of predicting/estimating plasma drug levels.

To address the above mentioned deficiencies a modified stirrer known as a crescent-shape spindle has been proposed, along with a simple mathematical approach, to evaluate dissolution characteristics of a product including predicting plasma drug levels. The suggested approach provides a simple, efficient and scientifically valid approach for dissolution testing as well as relating results to bioavailability characteristics of products in humans.

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Crescent-Shaped Spindle

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