These apparatuses:

1. Lack scientific merit and support. Experimental studies have shown that they will provide highly variable and unpredictable results because of poor product/medium interaction.




2. Cannot be qualified/validated using commonly used industry wide practices of qualifications for analytical instruments. In particular, they do not meet the requirements of design qualification (not fit for intended use) and operation qualification (cannot be qualified using a reference product).




3. Require meeting undefined and unqualified requirements such as de-aeration of the medium and control of vibration in and around the equipment.




4. Require drug and/or product dependent experimental conditions. Therefore, it will not be possible to know whether dissolution characteristics are a reflection of the products or of the experimental conditions used.




5. Do not differentiate between IR and ER products. The analyst must first know what type of release/dissolution to expect from the product and then use the experimental conditions design to provide the presumed released/dissolution characteristics.




6. Are routinely used for evaluating drug products for human use (e.g. pharmacopeial testing). However, they have never been validated to demonstrate that they can provide bio- or physiologically relevant results.




7. Are often used for quality control, and to check lot-to-lot consistency, purposes. However, a link of these apparatuses, and associated experimental conditions, to the quality of a product, and consistency thereof, is unknown or undefined. The only criterion used for this purpose is that the dissolution results must meet some arbitrary standards/tolerances. If the criterion is not met, it is assumed that the products may be of substandard attributes.




8. Are expected to provide discriminatory tests which should be capable of showing formulation/manufacturing differences among products and/or batches. On the other hand, it is a well known fact that these apparatuses frequently provide discriminatory results lacking any physiological significance or consequence.




9. Do not simulate in vivo or physiological environment (stirring and mixing) thus one cannot develop bio-relevant tests.




10.   Require tolerances be set lower than potency and content uniformity values, thus, results will reflect inaccurate and inappropriate quality of perfectly acceptable products.

Considering the above mentioned deficiencies, results obtained using these apparatuses can easily be questioned/challenged for their validity and relevance.

It is a well established fact, and often a regulatory requirement, that one has to demonstrate that an apparatus is capable of providing the intended and expected outcome. A simple and common example of this requirement is calibration of a laboratory weighing scale or balance. Initially when a balance is purchased, and then occasionally thereafter, it must be calibrated against reference weights to show that the balance can provide accurate weights of the references. If the balance does not perform as expected then it has to be adjusted accordingly. please click here for complete article

It is quite often asked which approach should one choose and why, i.e., is there a reason for the preference for one over the other?

Such a question has two components; (1) scientific or logical (2) required standards. Generally, the required standards component is based on the first one, i.e. science and logic. Unfortunately, in case of the current practices of dissolution testing, scientific principles are completely absent from the standardization. That is why there is so much difficulty, along with the associated frustrations.

I provide suggestions based on underlying scientific principles, which often do not fit well with the current practices, because, as I stated above, the current practices lack scientific reasoning and logic. People say that both MQ and PVT are good and valid, which is correct, and an analyst can choose either. However, the next question is, which one is better and why. That is where the difficulty is. If one likes to know which one is better, then one has to know the reason behind conducting these tests to start with, which will help in deciding and rationalizing the preferred one.

So, the question is why are these MQ and PVT done? The answer is, to establish that the apparatuses are fit for their intended purpose, i.e. apparatuses can be used to evaluate dissolution characteristics of a product for human use. The next question is, or at least should be, that if one meets the requirements of MQ/PVT, will the apparatuses be considered fit for the evaluation of the product for human use. The answer is clearly no, because both MQ/PVT lack the critical link between apparatuses and the evaluation of dissolution characteristics of a drug product (please use the link to read the article for further discussion). Therefore, in general, MQ and PVT are not useful practices and requirements, and are unnecessary burdens on the pharmaceutical industry.

Now if the testing (MQ/PVT) lacks any real benefit, but has to be performed to meet the requirement, then, I would prefer the MQ. The MQ takes the responsibility away from the analysts and transfers it to the vendors of the dissolution testers. They can provide certification that the testers meet the specifications, which they usually provide when one purchases an apparatus and may provide later as well. In addition, the beauty of MQ is that no one can question that an apparatus does not work/perform as expected, because there is no way to prove that it does not work, as performance of the apparatuses is not associated with the MQ requirements. So, my dear analysts, go with the MQ and say good bye to the PVT and its so called “best practices”.

This article provides a discussion based on data presented in literature that a direct comparison of dissolution results (profile) with blood levels (C-t profiles) can lead to misleading interpretation. For a more appropriate comparison dissolution results should first be converted to C-t (plasma drug conc.-time) profiles. Examples are provided for converting dissolution profiles, using convolution techniques, to C-t profiles which provide improved evaluation of dissolution results. The article also presents an argument, that for proper reflection of bio-relevancy of dissolution results, the tests require higher agitation (or product/medium interaction) relative to what is provided by the paddle apparatus at 50 and 75 rpm. please click here for complete article

The prediction of drug concentration-time (C-t) profiles in humans is highly desirable and needed for appropriate development of products and to establish their quality during production. A simple method to predict or estimate the C-t profiles, based on the convolution approach, has been suggested [link].

This article provides an application of the approach for the evaluation of metoprolol tartrate tablet products. Furthermore, it also demonstrates that the approach can be used to predict the C-t profiles for a sub-population as well. please click here for complete post

A commonly asked question is how one should select a dissolution apparatus. It may be of interest to know that, such a question is often asked when a dissolution analyst gets frustrated with the unexpected or unanticipated dissolution behavior of a test product. Such a question is seldom asked at the beginning of the project as it is always understood or assumed that one will most likely use a paddle apparatus. Furthermore, the analyst will try some variations of rpm (50, 75 or 100) or medium (different buffers and pHs). If this does not work, then perhaps the basket apparatus will be tried with similar variations in rpms and buffers. In the end, the analyst usually settles with a test which will provide the anticipated/expected characteristics of the test product. .(please click here for complete post)