Benznidazole-loaded multiparticulate drug delivery systems based on interpolyelectrolyte complexes for improving Chagas disease treatment

GARCÍA, MC.; MANZO, RH.; AOKI, MP.; JIMENEZ KAIRUZ, AF.

Rosario

Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticoas RICiFa 2016.; 2016

Fac. de Farmacia y Bioquímica, UNRos. y Fac. Cs. Qcas, UNC.

Chagas disease (CD) is caused by Trypanosoma cruzi infection and represents one of the most significant public health problems in Latin America. Benznidazole is the selected drug for treatment and it presents 60-80% parasitological cure rate. Nevertheless it shows very low solubility and several side effects (e.g. hepatotoxicity, hypersensitivity, bone narrow suppression, peripheral neuropathy) conditioning the efficacy and safety of pharmacotherapy. Multiparticulate drug delivery systems (MDDS) based on polymeric carriers are an interesting systems to improve the performance of BZ in CD treatment.The goal of this work was to development BZ-loaded MDDS based on interpolyelectrolyte complexes, and to characterize their physicochemical, pharmacotechnical and in-vitro biopharmaceutical properties. The MDDS were obtained by casting solvent (water and hydroalcoholic medium) and wet granulation. The polyelectrolytes selected were natural (chitosan-acid alginic) and synthetic (Eudragit´s). The MDM were characterized by determination of particle size, rheological ) properties, fluid up-take measurements?, confocal microscopy, X ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and in-vitro release. In addition, MDDS containing different combinations of the first ones were prepared and its in-vitro release properties were evaluated. The MDDS were obtained by a simple methodology with yields >90%. The particle sizes were 450-600, 600-850 and 850-1000μm. Their physicochemical properties showed adequate rheology characteristics for hard gelatin-capsule formulation. The FTIR exhibited ionic interaction between polyelectrolytes. Microscopy and XRD revealed free BZ on the surface of multiparticles. The dissolution profiles showed modulation in release, dependent on the composition of MDDS, from slow and controlled (Q120min≤40%) to very fast (Q15min>85%). The process of erosion-relaxation and swollen-diffusion were identified as the main mechanisms for BZ release, in accordance with the fluid up-take exhibited. The MDDS had good performance and their composition presented a high potential for designing multikinetic release systems, whose properties would be useful in the treatment of CD.