EVALUATION OF BINARY AND TERNARY SYSTEMS ON BIOPHARMACEUTICAL PROPERTIES OF FUROSEMIDE

JULIETA ABRAHAM MIRANDA; ARIANA ZOPPI; CLAUDIA GARNERO; MARCELA RAQUEL LONGHI; STERREN, VANESA B.

Congreso; Cuarta Reunión Internacional de Ciencias Farmacéuticas; 2016

Currently, supramolecular chemistry is intensely applied in the pharmaceuticalindustry with the purpose of optimizing the physicochemical and biopharmaceuticalproperties of active pharmaceutical ingredients (IFA). It is known that binary and ternarysystems, salts, cocrystals and amorphous solids are able to modify properties such assolubility, dissolution rate and permeability. An IFA commonly used in the treatment ofhypertension and edema is furosemide (FUR), which has highly variable oralbioavailability in humans due to its low solubility and permeability adding to its sitespecificabsorption in the stomach and upper small intestine. Previous studies revealedthat triethanolamine (TEA) is a permeation enhancer, while β-cyclodextrin (β-CD) andmaltodextrin (MD) showed capacity to increase solubility and dissolution rate of FUR.1,2In this study, with the aim of improving FUR dissolution, binary and ternary systemswere prepared and their effect on this property was analyzed.The solid-state systems FUR:TEA, FUR:TEA:β-CD and FUR:TEA:MD, in equimolarratios, were prepared by kneading method and physical mixture. These werecharacterized using infrared spectrometry (IR) and scanning electron microscopy (SEM).Moreover, their dissolution behaviors were evaluated in gastric simulated fluid withoutenzymes at 37.0 ± 0.5 °C.Characterization studies, by IR and SEM techniques, revealed molecular andmorphological differences between the solid samples obtained and their individualcomponents. Also, the dissolution profiles of binary and ternary systems showed anincrease in dissolution rate and percentage of drug dissolved compared to free FUR. It isinteresting to note that only 12% of the drug was dissolved in free FUR, while in binarysystem we observed a 16% dissolved and a 34% in both ternary systems in the sameexperimental conditions. Demonstrating that by formulating FUR in these systems wesignificantly improved the dissolution rate. The enhancement in this property may beattributed to an increase of solubility.In conclusion, the ternary systems have shown promising results and could constitutean alternative for improving the bioavailability of FUR.