Dissolution Apparatuses: Compliant vs Qualified and Validated

There appears to be serious and unfortunate confusion among the dissolution scientists/analysts, which implies that the compliance and qualification/validation of apparatuses are one and the same or at least interchangeable. This is incorrect. The data obtained using apparatuses such as pharmacopeial paddle/basket, which usually are in compliance but NOT qualified/validated. They have limited scientific validity and lack relevance to products’ attributes or qualities, as explained below:

A compliant apparatus means that it meets the required specifications commonly set by standard-setting organizations (such as pharmacopeias, e.g., USP 1 & 2) for the manufacturing and operating of the apparatuses. On the other hand, a qualified and validated apparatus can be used for its intended purpose to evaluate or assess, reproducibly, the product’s characteristics, which in this case is drug dissolution testing. The qualification/validation step usually requires a reference (product) with known characteristics, established independently of the apparatus. It is generally assumed that if an apparatus complies with the required specifications, it is qualified and validated as well. This is often the case, but not with dissolution apparatuses. No reference product is available with known dissolution characteristics established independently, so one cannot qualify and validate these apparatuses. If one cannot qualify and/or validate a dissolution apparatus, one cannot determine the test product’s dissolution characteristics either.

Interpretation of dissolution results obtained from such apparatuses will be misleading at best and incorrect in general. A quick and simple method to assess the qualification and validation of a dissolution apparatus without a reference product is to conduct a comparative dissolution test using IR and ER products of the same drug. The IR and ER products have known dissolution characteristics independently established using human bioavailability studies.

A qualified and validated apparatus will be the one that will differentiate the drug dissolution characteristics of these products using a common set of experimental conditions simulating the GI tract environment. A qualified and validated dissolution apparatus can be compliant by including its specifications in a pharmacopeia. However, current compliant apparatuses cannot be made qualified and validated, in particular paddle/basket, as they lack the capability of providing relevant and reproducible dissolution results.

The use of a qualified and validated dissolution apparatus, which may not have compliance specifications, will be more appropriate at present for the development or evaluation of products than the one which has compliance specifications but has not been qualified and validated. The crescent-shaped spindle has been developed to address the deficiencies of the currently used apparatuses and practices to provide a more appropriate choice for conducting dissolution testing and, thus product development and evaluation.

Related Posts