An Alternative Methodology to Evaluate Dissolution Similarity. The Intra-Batch Variation Rule for f2

MENDIZÁBAL, M. C.; MAGGIO, R. M.; KAUFMAN, T. S.

Córdoba

Congreso; Ricifa III; 2014

RICIFA

Dissolution test is an usefultool to ensure the qualityof a drug product during the stages of development and production of solid dosage forms. Difference (f1) and similarity (f2) factors proposed by Moore and Flanner are an example of model independent methods for the comparison of dissolution behavior; to this end,f2is the most used approach. The f2factor is a mathematical transformation of the difference between dissolution profiles (mean of 12 curves) of test and reference formulation. However, f2has several disadvantages; among them it ignores variability of the individual dissolution curves within each batch, since it is calculated from the dissolution profile. For this reason we proposean improvement of the f2methodology, where each curve is used for comparison. The fact of taking into account the data distribution within batch is an emerging advantage over the traditional method. The strategy proposed for the evaluation ofthe dissolution of two batches can be divided in two stages. In a first instance, the f2 is calculated among all reference curves. Using these values, a lower limit of acceptance for f2 (LLAF) is set, given by the condition that 97.5% of the calculated f2 values are above this limit.In a second instance, the f2values are calculated among all reference curves and all test curves. This set of f2 values are individually compared with the LLAF calculated in the first stage. The rule of acceptance is that at least 80% of the reference-test f2values must be above the LLAF. The proposed methodology was validated with dissolution data of two batches each of four commercial brands (totalling 8 batches) of hydrochlorothiazide tablets. Comparing the traditional f2-based determination with the proposed method, few discordant datapoints were found.