EVALUATION OF BINARY AND TERNARY SYSTEMS ON BIOPHARMACEUTICAL PROPERTIES OF FUROSEMIDE

ABRAHAM MIRANDA J; GARNERO C; STERREN V; ZOPPI A; LONGHI MR

Rosario

Congreso; IV Reunión Internacional de Ciencias Farmacéuticas; 2016

Currently, supramolecular chemistry is intensely applied in the pharmaceutical industry with the purpose of optimizing the physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (IFA). It is known that binary and ternary systems, salts, cocrystals and amorphous solids are able to modify properties such as solubility, dissolution rate and permeability. An IFA commonly used in the treatment of hypertension and edema is furosemide (FUR), which has highly variable oral bioavailability in humans due to its low solubility and permeability adding to its site-specific absorption in the stomach and upper small intestine. Previous studies revealed that triethanolamine (TEA) is a permeation enhancer, while β-cyclodextrin (β-CD) and maltodextrin (MD) showed capacity to increase solubility and dissolution rate of FUR.1,2 In this study, with the aim of improving FUR dissolution, binary and ternary systems were prepared and their effect on this property was analyzed.The solid-state systems FUR:TEA, FUR:TEA:β-CD and FUR:TEA:MD, in equimolar ratios, were prepared by kneading method and physical mixture. These were characterized using infrared spectrometry (IR) and scanning electron microscopy (SEM). Moreover, their dissolution behaviors were evaluated in gastric simulated fluid without enzymes at 37.0 ± 0.5 °C.Characterization studies, by IR and SEM techniques, revealed molecular and morphological differences between the solid samples obtained and their individual components. Also, the dissolution profiles of binary and ternary systems showed an increase in dissolution rate and percentage of drug dissolved compared to free FUR. It is interesting to note that only 12% of the drug was dissolved in free FUR, while in binary system we observed a 16% dissolved and a 34% in both ternary systems in the same experimental conditions. Demonstrating that by formulating FUR in these systems we significantly improved the dissolution rate. The enhancement in this property may be attributed to an increase of solubility.In conclusion, the ternary systems have shown promising results and could constitute an alternative for improving the bioavailability of FUR.Keywords: furosemide, supramolecular systems, dissolution.1. Garnero C, Chattah AK, Longhi M., Carbohyd. Polym. 2013, 94, 292-300.2. Garnero C, Chattah AK, Longhi M., J. Pharm. Biomed. Anal. 2014, 95, 139-145.