IMPROVING THE SOLUBILITY OF FUROSEMIDE

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

Congreso; Cuarta Reunión Internacional de Ciencias Farmacéuticas; 2016

Furosemide (FUR) is a drug used in the treatment of hypertension and edema. FUR isclassified as class IV in the Biopharmaceutics Classification System due to its lowaqueous solubility and poor intestinal permeability. At the same time, FUR has a tendencyto undergo site-specific absorption in the stomach and upper small intestine. Theseproperties lead to a highly variable oral bioavailability of FUR in humans (20-60%).1Innovative systems that increase solubility could be a useful strategy to increase oralbioavailability and decrease variability. Therefore, with the aim of enhancing FURsolubility, we evaluated the effect of binary and ternary systems have on its solubility inwater and gastric simulated fluid (FGS).Experiments were carried out according to the Higuchi & Connors metod.2 Binarysystems were obtained with different ligands such as valine, leucine, isoleucine, arginine,aspartic acid, glutamic acid, and triethanolamine, while for ternary systems arginine ortriethanolamine with addition of β-cyclodextrin or maltodextrin were used. The tubeswere placed to constant agitation at 37.0 ± 0.5 ºC for 72 h. After equilibrium was reached,the suspensions were filtered and the filtrate was appropriately diluted for quantitativeanalysis of FUR by UV?Vis spectrophotometry. The apparent stability constants werecalculated.The results showed that solubility of FUR in water, in binary systems, was increasedwith arginine and triethanolamine. However, binary systems did not improve solubilityin FGS, this may be due to FUR ionization. This drug was ionized in water and neutral inFGS, suggesting that interactions in water were ionic. In the case of ternary systems, FURmaintained the aqueous solubility observed in the binary ones. By contrast, ternarysystems containing maltodextrin significantly increased the solubility in FGS, whereby itcould be suggested that neutral FUR was encapsulated by maltodextrin.In conclusion, these structures constitute an alternative to improve FUR solubility withpotential application in the optimization of its oral bioavailability.