SOLID DISPERSIONS AS A PHARMACEUTICAL STRATEGY FOR CARRING BENZNIDAZOLE

ANALÍA IRMA ROMERO; ELIO EMILIO GONZO; SANTIAGO NICOLÁS CAMPOS; MERCEDES VILLEGAS; ALICIA GRACIELA CID; JOSÉ MARÍA BERMÚDEZ; CINTIA ALEJANDRA BRIONES

Mar del Plata

Otro; Reunión Anual de SOCIEDADES DE BIOCIENCIA; 2019

Solid dispersions (SD) are considered one of the most successful strategies for improving the dissolution of poorly soluble drugs. Benznidazole (BZL) is a antiparasitic agent with low water solubility, used as a first-line drug for the treatment against Chagas disease. The aim of this work was to evaluate the dissolution properties of BZL from SD based on Gelucire® and poloxamer. SD based on Gelucire® 44/14 (G4414) were prepared by a modification of the fusion method with 20, 40 and 50 %w/w BZL loads (DS G4414-20, DS G4414-40 and DS G4414-50, respectively). A SD using a mixture of G4414 and poloxamer 407 (P407) (1:1) with 40%w/w BZL load was also prepared. SD morphology was compared with the corresponding physical mixture by scanning electronic microscopy (SEM), and the dissolution profiles were obtained at 37°C using 0.1 N HCl as dissolution medium. The data were adjusted by the Lumped model, a mathematical model developed and validated by our research group, which allowed to calculate the initial dissolution rate (DRi), the time needed to dissolve 80% of the drug (t80%) and the dissolution efficiency (DE). SEM revealed that drug crystals were not distinguished in the SD, whereas they were clearly present in the corresponding physical mixtures, confirming that the BZL was dispersed in an amorphous matrix. The data from the dissolution profiles were properly adjusted using the Lumped model (R2>0.89). Not only the DRi but also the amount of BZL dissolved were improved when formulated in a SD, and decreased along with an increase in the BZL load. The SD based on the mixture of G4414 and P407 showed the greater DRi (13.70 mg/min), which was 16 times higher than the DRi of the free drug. It can be concluded that the SD developed are promising to formulate an extemporaneous suspension of BZL with adequate biopharmaceutic properties, what would lead to better oral bioavailability in the treatment against Chagas disease.