Dissolution Apparatuses: Compliant vs Qualified and Validated

It appears that there is 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 interchangeable. This is incorrect. The data obtained using apparatuses such as pharmacopeial paddle/basket, which usually are in compliance but NOT qualified/validated, 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 <711>) for the manufacturing and operation of the apparatuses. On the other hand, a qualified and validated apparatus means that it can be used for its intended purpose to evaluate or assess, reproducibly, the characteristics of the product which in this case is drug dissolution testing. The qualification/validation step usually requires a reference (product) with known characteristics, established independently to the apparatus, which is to be qualified or validated.

It is generally assumed that if an apparatus is in compliance with the required specifications, then it is qualified and validated as well. This is often the case, but not with the dissolution apparatuses. As there is no reference product available with known dissolution characteristics, established independently, one cannot qualify and validate these apparatuses. If one cannot qualify and/or validate a dissolution apparatus, one also cannot determine dissolution characteristics of the test products 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, in the absence of a reference product, is to conduct a comparative dissolution test using IR and ER products of the same drug. The IR and ER products represent having the known dissolution characteristics which are independently established using human bioavailability studies. A qualified and validated apparatus will be the one which 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 made 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 shape 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 products development and evaluation.

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