Author: Dr. Saeed Qureshi, Ph.D.

Please do not spend too much time thinking or discussing dissolution results, as currently suggested testers and experimental conditions have no scientific basis. In addition, dissolution testing using currently suggested apparatuses, particularly paddle/basket, provides only highly variable, unpredictable, and irrelevant results.

If you do not get the expected or desired results, please keep testing until you get the desired results, which is the pharmacopeial approach of continued testing (S1 to S3) with six units, followed by six more units, and then by 12 units. You will be in a tough situation if you do not meet the test at S3. After that, you might have to make up some clever suggestion/reason to get over this situation so that you can continue this repetitive testing.

In the end, if you have a choice, document that the suggested testers are non-GMP (non-validated/non-qualified). Thus, their use was not further explored. No one can challenge this! Instead, use a more scientifically relevant tester, e.g., see here.

There are a number of reasons why one can use, in fact, should use, non-compendial testers and methods, e.g., when currently recommended compendial testers/methods are:

  1. Unable to determine dissolution characteristics of a blinded sample, a common and standard practice/requirement for any analytical test.
  2. The usefulness (validity) of the tester/method is in question, i.e., a tester/method is not capable of determining and differentiating dissolution characteristics of products. For example, they cannot differentiate between immediate- and extended-release products having the same active ingredient.
  3. The underlying science is weak or invalid, e.g., the test method is product-dependent. It is a severe scientific violation that the method used is product-dependent.
  4. Complex and time-consuming.

Pharmacopeial testers/methods are deficient in all the above-mentioned characteristics/requirements. Therefore, if a newer approach addresses any or all of the above-mentioned deficiencies, then automatically, the new or modified tester/method becomes superior and should be used. Therefore, people should focus on addressing and improving current methods and proactively suggest newer methods to the agencies. Analysts/scientists should not consider views that only pharmacopeial testers/methods should be employed to avoid potential delays in product approval. Spending some extra time upfront to have a scientifically valid and robust method is much better. Rather than using the recommended method/approach, which is flawed as it will cost a lot more during production cycles, failures (OOS), recall, etc.

It is important to note that modified testers/methods should be suggested at the product application stage, where it would be relatively easier to accept. It is highly unlikely to change at the production or plant inspection stage, as specifications are part of the “contract,” which are very difficult or impossible to change.

The Crescent-shaped spindle (link) has been suggested for drug dissolution testing to address the deficiencies of the currently recommended apparatuses and methods. In addition, its use significantly reduces the workload, thus increasing efficiency and cost savings.