IMPROVING THE SOLUBILITY OF FUROSEMIDE

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

Rosario, Santa Fe

Congreso; 4a Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2016

Furosemide (FUR) is a drug used in the treatment of hypertension and edema. FUR is classified as class IV in the Biopharmaceutics Classification System due to its low aqueous solubility and poor intestinal permeability. At the same time, FUR has a tendency to undergo site-specific absorption in the stomach and upper small intestine. These properties 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 oral bioavailability and decrease variability. Therefore, with the aim of enhancing FUR solubility, we evaluated the effect of binary and ternary systems have on its solubility in water and gastric simulated fluid (FGS).Experiments were carried out according to the Higuchi & Connors metod.2 Binary systems were obtained with different ligands such as valine, leucine, isoleucine, arginine, aspartic acid, glutamic acid, and triethanolamine, while for ternary systems arginine or triethanolamine with addition of β-cyclodextrin or maltodextrin were used. The tubes were 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 quantitative analysis of FUR by UV?Vis spectrophotometry. The apparent stability constants were calculated.The results showed that solubility of FUR in water, in binary systems, was increased with arginine and triethanolamine. However, binary systems did not improve solubility in FGS, this may be due to FUR ionization. This drug was ionized in water and neutral in FGS, suggesting that interactions in water were ionic. In the case of ternary systems, FUR maintained the aqueous solubility observed in the binary ones. By contrast, ternary systems containing maltodextrin significantly increased the solubility in FGS, whereby it could be suggested that neutral FUR was encapsulated by maltodextrin.In conclusion, these structures constitute an alternative to improve FUR solubility with potential application in the optimization of its oral bioavailability.