DEVELOPMENT AND VALIDATION OF A DISSOLUTION METHOD FOR BENZNIDAZOLE TABLETS BASED ON FACTORIAL DESIGN

Abstract

Dissolution is the rate-limiting step for the bioavailability of drugs belonging to Class II of the Biopharmaceutical Classification System. Given this, the present study aimed to establish the optimal conditions for performing the dissolution test of benznidazole (BNZ), an essential drug in the treatment of Chagas disease. Initially, the solubility of BNZ was determined in water, simulated gastric fluid (SGF), 0.1 M HCl, and in media supplemented with surfactants (sodium lauryl sulfate - SLS and Tween 80) at concentrations of 0.5%, 0.75%, and 1%. To optimize the dissolution test conditions in the medium that promoted the highest solubilization (SGF with SLS), a factorial design was applied, varying the SLS concentration (0.75% and 1%), media volume (500 mL and 1000 mL), and paddle rotation speed (75 rpm and 100 rpm). The conditions that presented the most favorable profile consisted of using 1000 mL of SGF supplemented with 1% SLS at a rotation speed of 75 rpm. The UV-Vis spectrophotometric analytical method and the dissolution method were properly validated, demonstrating linearity, precision, accuracy, selectivity, and robustness, confirming their safe applicability in the routine quality control of BNZ tablets.