The purpose of a dissolution tester is to test a tablet/capsule product for its potential dissolution characteristics in the human GI tract. In general, it is now well recognized that the currently used dissolution testers, in particular paddle and basket, do not provide such dissolution characteristics. In fact, they cannot provide dissolution characteristics because of the flaws of poor product/medium interaction within the apparatuses. Therefore, these apparatuses cannot be qualified and/or validated as dissolution testers and thus cannot be used to develop and evaluate the products.
The practices of the past many years have been to keep using these apparatuses for product development and evaluation (isn’t this bizarre?) with a change/twist in the objective of dissolution testing by calling it a quality control test. However, how does one link the dissolution test to the quality of the product when it requires its link to the dissolution characteristics in vivo, i.e., human GI tract? Oops, there is no link here, as stated in the paragraph above.
The objective of the testing should be twisted again. This time it would be called testers/testing for batch-to-batch consistency check. As the link or relevance of the test to its original and actual objective has been severed, but the same testing is still required to be done. Therefore, certain practices (“rituals”) have to be suggested to come up with some standards, any standard, that everyone has to follow. Presently, this standard is called Q-Value (to make it sound professional!), which is 80/30, i.e., 80% of the drug should dissolve within 30 minutes. Where did this number, 80/30, come from? One is not expected to ask or know! One just has to accept it. However, one can negotiate this number, based on one’s negotiating skills, to get another number for one’s product say, 70/45 or 75/20 or any other.
Now there is a problem: it is often difficult to meet this standard (80/30 or a different one) because the tester itself is highly variable in nature. One cannot obtain repeatable and reproducible results within the expected norms.
So, what should one do now? Let us introduce a Performance Verification Test (PVT) to test the tester. What is a PVT? It is a dissolution test, using in-house developed tablets, which everyone is expected to conduct to get one’s own product approved. How does this PVT help in improving the tester? No one knows. It is assumed that the PVT establishes: the validity of a vibration-free environment in and around the tester, the de-aeration content of the medium, the perfectness of the vessel dimensions, and its alignment. Oops, what happened to the evaluation of the performance of the tester? Does it improve the repeatability and reproducibility of the testers? Of course not, because the issue of repeatability and reproducibility relates to spindle/vessel combination remains the same, so remains the problem.
So, what should be done now? Let us get rid of this PVT. It causes too much hassle and frustration. Let us have something else and call it the Enhanced Mechanical Qualification (EMQ or simply MQ). What is the MQ? It is a set of (same old) physical specifications but with somewhat tighter tolerances. Now everyone is required to get certified that the tolerances are within the expectations. How does MQ establish or improve the performance of the tester? It does not. It is assumed that if one has certificates and good record keeping, the performance of the testers will be considered (assumed) improved or OK. But the lack of performance, or flaws, was not because of the broader tolerances. It is because the combination of spindle/vessel. As the spindle/vessel combination remains the same, so does the problem. However, one will not see the problems anymore, as there is no performance test associated with MQ. Therefore, the idea is if one does not see the problem, it is safe to assume that the problem does not exist. So, how could the MQ help? It does not.
What should be done now? Develop a performance qualifier for the PVT and/or MQ. What is a performance qualifier? It is a piece of equipment that perhaps costs many thousands of dollars, which will help show that the apparatus is within required specifications. The question is, why would the specifications change when the manufacturers provide all the certifications. Remember, you are not supposed to ask questions! Will this performance qualifier help? Of course not, because it was never a specification issue, tight or broad, so how it can be addressed or solved. It does not.
Specifications were correct all along. These are the same apparatuses/testers with practically the same specifications and tolerances, but maybe with some tweaking for personal gratification, otherwise nothing has changed.
We started with the use of these apparatuses as dissolution testers but generated a whole new industry of the performance verification/validation and qualification, which is based on made-up requirements of MQ and PVT for monitoring irrelevant and useless parameters.
Let us hope that this practice stops here. If you ask my opinion, then I will say that brakes have already been applied to use paddle and basket apparatuses. It is just taking time to formalize and generalize it. People have already started evaluating other alternatives because current apparatuses are not qualified and validated for the intended purpose and thus, the results obtained from them cannot be trusted.