Desenvolvimento de um sistema de liberação controlada pH-dependente para o Antichagásico Benznidazol usando a Laponita como carreador e revestido com Eudragit® S100

Abstract

Benznidazole (BNZ) is an approved drug used for the treatment of Chagas disease, or American trypanosomiasis, an endemic Latin America illness that affects chronically thousands of people. The low drug solubility in gastrointestinal environments demands high daily dosages. Thus, the safety and efficacy of the treatment are compromised by the side effects. A convenient alternative to improve the biopharmaceutical properties is the development of low-cost pH sensitive drug delivery systems with easy execution for the incorporation of drugs. In this study, BNZ was incorporated into the laponite synthetic clay (LAP) via hot melt loading method. Then, the hybrid LAPBNZ was encapsulated with EudragitⓇ S100 (ES-100) by solvent evaporation coating technique. The materials were characterized by X-ray Diffraction (XRD), X-ray Fluorescence (XRF), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDS). The results indicate an efficient drug-loading rate into LAP and also an effective polymeric coating layer. Interestingly, in vitro release profile was about only 11.4% in the stomach simulated region; 23.8% in the first intestinal simulated region and 53.2% in the second simulated intestinal region. Thus, about 88.4% were released after 12 hours in a prolonged and pH-responsive manner. In addition, a kinetic study was carried out and the experimental data were best described by the KorsmeyerPeppas model. This result indicates a Case II of diffusional release mechanism, typical for the synthetic clay and conditions studied. The new drug delivery system reported here is expected to be useful in future formulations.