Técnicas de remuestreo en la comparación de curvas de disolución de fármacos

According to the current Guidelines (EMEA and FDA/CDER) dissolution studies are always necessary and consequently required. Dissolution assays can serve several purposes: (i) during the development of a medicinal product a dissolution test is used as a tool to identify formulation factors that are influencing the bioavailability of the drug; (ii) in the quality control of scale-up and of production batches, a dissolution test is used to prove consistency in the manufacturing and to ensure that the dissolution profiles remain similar to those of pivotal clinical trial batches; furthermore, (iii) in bioequivalence surrogate inference a dissolution test can be used to demonstrate similarity between different formulations of an active substance and the reference medicinal product. Regulatory interest in dissolution profiles comparisons is in knowing how similar the curves are, and to have a measure sensitive to large differences at any particular time point. Similarity factor f2 is gaining popularity due to its recommendation by various regulatory committees as a criterion for the assessment of the similarity between two dissolution profiles. The aim of this study was to develop theoretical and simulation studies to assess by means of bootstrap confidence intervals for f2, the sameness of dissolution profiles.