A recent query!


How i can enhance Pioglitazone Hydrochloride dissolution profile results in combination with metformin HCl tablet ????

My response:

It is a common question/issue i.e. people ask that they do not observe expected or desired drug dissolution characteristics of a product, but faster or slower. The simple and direct answer to such a question should be to change/adjust the product formulation/manufacturing attributes accordingly. In fact, that should be the only option or advice provided. Often as one does not know the formulation (usually not disclosed), thus it is impossible for anyone to provide any useful advice in this regard.

On the other hand, at present, formulators have been convinced and/or trained to seek changes or adjustments in the dissolution method itself to obtain the characteristics they like to see. Such a practice of dissolution method adjustments are commonly promoted as science and method development practices. I call this as “Fashionable Nonsense”, as this practice is neither scientifically valid nor of any practical use (link). So please avoid such a practice.

To address such a problem/question, I would ask how you would know that your dissolution observations/results are correct. Is your method capable of providing accurate and/or valid dissolution results? That is, is the method you used has been validated to determine dissolution characteristics of a product? The answer is NO, i.e., none of the testers/methods, as recommended at present, are qualified and/or validated for dissolution testing. Thus, one cannot determine dissolution characteristics of any product (link). The dissolution results what you are seeing are simply an illusion, not actual or true dissolution characteristics of the product. Therefore, it is not possible to address the problem using currently recommended testers/methods. This is hard to believe but it is a scientific fact.

Considering this background, I have suggested a modified stirrer, known as crescent-shape spindle, based tester which addresses the issues and provide far better dissolution testing and product characterization. You may read the details about it here. If you require further information, I will be happy explain it further.
Best of luck!

Scientifically speaking!

Link for relevant discussion (1)

Fashionable Nonsense

Some links for relevant discussion (1, 2, 3)

Drug Dissolution Testing – A Query

You may send your response to principal@pharmacomechanics.com

Using techniques, such as IVIVC, PBPK, and/or other sophisticated statistical analyses, to show validation of dissolution testers and/or their ability to predict in vivo performance is a false science and of no practical use

It is often argued that validation of dissolution tests/testers can be, or have been, achieved using IVIVC based on convolution/deconvolution (CON/DECON) methods, and more recently applying PBPK (Physiologically Based Pharmacokinetic) modelling/simulation techniques. Unfortunately, this is scientifically incorrect and an invalid view and practice.

In reality, CON/DECON and PBPK techniques are mathematical/statistical techniques which use in vitro and in vivo results obtained experimentally. While applying the mathematical techniques, mathematicians/statisticians make a fundamental assumption that the data/results provided to them are relevant and valid, obviously obtained using qualified and/or validated tests and testers. It is the analytical laboratory which ensures that the results were obtained using qualified and validated tests and testers. The important thing to note here is that CON/DECON and PBPK are applications, mostly software, used to transform in vitro results into in vivo. They are not to show or prove that testers/tests used were validated or qualified, but work on the assumption that testers/tests were appropriately validated. Stating that CON/DECON or PBPK techniques establish that dissolution results were obtained using validated/qualified tests/testers is scientifically invalid view and unfortunately reflects misunderstood concept of the mathematical/statistical techniques applied.

It is of utmost importance to note that before using dissolution results for any purpose – eyeballing, similarity factor, tolerances setting, QC/QA, CON/DECON, PBPK or any other sophisticated statistical analyses – one has to establish that results obtained were from qualified or validated tests/testers. This qualification/validation has to be done PRIOR and INDEPENDENTLY, and not using products under development or assessment. If dissolution testers provide irrelevant and erratic results, which they do especially paddle and basket, then any modelling or statistical technique will not help in getting relevant results or correcting the problem. It will be complete waste of time and resources. One must first focus on developing and using qualified and validated dissolution testers.

In short, as the currently recommended testers have never been qualified and validated independently, thus use of techniques mentioned such as CON/DECON, PBPK, simulation/modelling, and other statistical analyses, becomes void and are of no practical use. Therefore, one must first focus on establishing or developing qualified and validated dissolution testers, if valid and successful use of IVIVC or PBPK is desired

Crescent-Shaped Spindle

Now Available
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