CENTRO DE INVESTIGACION Y DESARROLLO EN CIENCIAS APLICADAS "DR. JORGE J. RONCO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Relevancia biofarmacéutica de los métodos para comparar perfiles de disolución
MARÍA ESPERANZA RUIZ
Workshop; I Workshop "Dissolution testing and Bioequivalence"; 2013
Universidad Nacional de La Plata - American Association of Pharmaceutical Scientists
The performance of the main methods proposed for the comparison of percent dissolved vs. time curves were analyzed comparatively, to propose a more biorrelevant combined-approach for the comparison of dissolution profiles of multisource drug products. In vitro dissolution tests of four brands of Oxcarbazepine (OxCBZ) and four brands of Acenocoumarol (ACM) tablets were performed, and the resulting profiles were compared by model independent, model dependent and ANOVA-based statistical methods. After a careful analysis of the results, some methods were chosen and applied to the comparison of dissolution profiles of four brands of Carbamazepine (CBZ) tablets and two brands of Phenytoin (PHT) capsules. Finally, these in vitro results were qualitatively correlated with the corresponding in vivo results previously obtained with the same CBZ and PHT products assayed in healthy volunteers. The analysis of the dissolution data obtained with OxCBZ and ACM tablets allowed discarding the ANOVA-based statistical methods, since in all cases they were over-discriminating from a biopharmaceutical point of view, as well as the model-dependent methods, since it was not possible to fit dissolution data of multisource products to the same equation, and thus the comparison could not be done. When the remaining comparison methods (model-independent) were applied to in vitro profiles of CBZ and PHT products and the results correlated with in vivo data, the best correlations were found when the result of the f2 similarity factor was combined with a measure of the dissolution extent (e.g., area under the curve). This combined approach gives a robust and informative result, with the most biopharmaceutical relevance.