Product dependent dissolution testing – a scientifically invalid practice

It is often suggested that as drug release mechanisms may differ from product to product dissolution tests, conditions/methods should also be product-dependent to reflect these differences in drug release mechanisms. Often, such reasoning is provided for extended-release products and, strangely enough, not for immediate-release products. For example, recently (Link, Feb. 2011 issue, Q&A section), such an opinion is provided for nifedipine extended-release tablet products. In reality, however, it is not a correct view and is scientifically invalid as well.

A drug dissolution test does not have a link to the mechanism of drug release of a product. Thus it would not be able to differentiate the mechanism. A dissolution test only measures the amount of drug present in solution form at a specific sampling time. Perhaps the following analogy may explain it better. Monitoring (measuring) the speed of a moving vehicle using a speed gun (radar) does not depend on the type of engine (V4, V6, or V8) or size (car, van, bus, or truck) of the vehicle or type of the fuel (petrol or diesel) the vehicle uses. A speed gun works on the principle of monitoring change in distance per unit time. It is immaterial whether the change in distance is produced by different engine types or vehicle types (car or bus). Similarly, a dissolution test measures drug concentration in a dissolution medium with time, irrespective of the mechanism of drug release such as osmotic-based, diffusion-based or any other type. A dissolution test only reflects the drug in solution at a given sampling time.

On the physiological side, absorption is also independent of the drug release mechanism of a product. Drug absorption, or levels in the blood, depends on the drug in solution form in the GI tract, not how (a mechanism) it is delivered. If a drug is released slowly from the product, then dissolution will be slowed thus, absorption will be slow, irrespective of the release mechanism and vice versa.

Furthermore, the dissolution test conditions (medium, temperature, mixing) mimic the GI tract (intestinal) environment, not the product type or its delivery mechanism. As the GI tract environment remains constant from product to product, dissolution testing environments must also remain constant, otherwise a dissolution test should be considered void.

It is to be noted that the use of product-dependent experimental conditions are employed to accommodate the use of paddle and basket apparatuses which are known to be flawed because of their poor mixing and stirring characteristics. These apparatuses are not capable of providing the required product independent dissolution testing. As a result, product-dependent dissolution testing is a practice that produces useless dissolution data and puts an enormous and unnecessary burden on the pharmaceutical industry and regulatory agencies.

It is hoped that standard-setting organizations will discourage and/or consider discontinuing the current practices of product-dependent dissolution testing.

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