It may be said that analysts performing drug dissolution tests are in a pretty difficult situation. They are expected to conduct appropriate dissolution tests to determine the quality of a product based on its in vitro drug release characteristics. However, procedures described in the literature (e.g. USP <1092>) or commonly taught in courses provide suggestions for choosing/selecting experimental conditions to achieve (match) a desired or pre-set dissolution outcome. These desired dissolution characteristics are commonly obtained by selecting apparatuses (mostly between basket and paddle) and/or by adjusting rpm, pH or molarity of medium/buffer and/or solubiliser (nature or amount). Therefore, it is important to note that the analyst, following the currently suggested procedures, will never know the true or actual nature of drug dissolution characteristics of the product, thus its quality. Continue reading →

The USP in general, and its Biopharmaceutics Expert Advisory Committee (EAC) in particular, has been at the centre of developing standards and procedures for drug dissolution testing for the past three decades. However, this EAC has been dissolved for the coming cycle (2010-2015) of the USP expert committees. The activities/responsibilities of the now-dissolved EAC have been transferred to a committee for General Chapter on Dosage Forms, with very few members from the earlier EAC. There has been lack of clear information from the USP on this particular change, especially at a time, when the dissolution community is seeking answers for the difficult and frustrating problems related to the drug dissolution testing. Often, these relate to the use of drug dissolution testing for product evaluations and the use and relevance of PVT.

 In the absence of clear information and an apparent significantly diminished role in the future, one can only speculate on the possible scenarios. One of those could be that the USP may be reducing its laboratory based activities (research?) in the dissolution area as there has been limited or no success, but rather frustrations, during the past number of years. The USP may be reversing to a more traditional role for setting objective standards based on the contributions from external sources. If this assumption is correct, then the change at the USP may be considered good. This will provide the industry and others to make needed contributions and for the USP an approach for critically evaluating the problems and accepting the solutions.

Sub menu “List of Publications” has been changed to “Useful Lists” as there will be more than one list under this sub-heading which will include the publications list (appears quite popular and frequently downloaded). A new list has been added to include titles of the posts with hyperlinks for your convenience of access and reading. 

Your interest in our website is highly appreciated and we look forward to your feedback and suggestions for improvement. Please submit your comments and suggestions to the moderator.

Like any other analytical test, a dissolution test must also be repeatable and reproducible, with a reasonable/acceptable variability as reflected by RSD (or CV) values, say within 5 to 10%. This acceptable variability should be based on a reference product (e.g. PVT) and obtained from a multi-lab evaluation.

It has been shown from experimental studies, and computer simulation models, that such a desired variability is not possible to obtain using the current apparatuses, in particular paddle/basket. Recent discussions of unexplained high failure rate of PVT are also a reflection of high variability in testing. Therefore, in general, it is not possible to rely on such a highly variable method to establish consistency of the product quality.

As a common practice, analysts prefer to use compendial methods, if available, to evaluate pharmaceutical products. There are clear advantages of using such methods, as the results obtained are easier to be accepted by third parties including regulatory agencies.

On the other hand, in some cases, where compendial methods lack desired characteristics or found to have flaws, then such a practice seriously hampers the appropriate testing and thus proper evaluations of the products. This leads to significant frustrations on analysts’ part as well as demands for a large resource (human and financial) burden on the pharmaceutical industry. Continue reading →

The objective of drug dissolution testing is to determine drug release characteristics of a product i.e. how fast or slow a drug would be released from the product reflecting its formulation and/or manufacturing attributes (properties).

In reality, however, current practices of dissolution testing seek product dependent experimental conditions, based on choices of apparatus, rpm/flow-rate and medium (its pH and strength) to attain a desired or expected dissolution rate. “True” dissolution characteristics of a product can never be known. Using current practice or approach, often multiple dissolution methods are described for the same product under different names such as bio-relevant method, discriminating method, QC method, USP method, FDA method, etc. differing in experimental conditions, each providing different dissolution results.

That is why, it is commonly referred that one should consult the authorities to establish the method and to determine if the results would be acceptable to the authorities.

For establishing “true” dissolution characteristics, like any other analytical method, a dissolution method must be product independent. Developing a product independent test leading to determining “true” dissolution characteristics of a product is relatively simple which would save significant financial and human resources compared to the current practices. For further discussion on this aspect, please see the article and details of the upcoming seminar.