Characterization of a quatyernary liquid system improving the biovailability of poorly water soluble drugs

The aim of this work is the characterization of the quaternary system composed of water, triacetin (oil), ethanol (alcohol), and Tween 80 (surfactant), as its results enable the enhancement of the bioavailability of nimesulide, a poorly water soluble nonsteroidal antiinflammatory drug widely employed in the pharmaceutical field. Particular attention is devoted to the surfactant-free ternary system, as it proved able to solubilize nimesulide as well, and the absence of a surfactant is desirable in order to keep the preparation as tolerable as possible. Both bulk and interfacial properties of this system are investigated, and a mathematical model to calculate the interface composition of a threecomponent two-phase system is developed. This model is based on Gibbs’ theory on interfaces, which considers an arbitrary mathematical dividing surface so that the two phases continue uniformly up to it, although interface regions have no sharply defined boundaries. We find that both the quaternary and the ternary systems investigated show a miscibility lacuna and that, in the surfactant-free ternary system, an increase of the ethanol weight fraction is reflected as an impoverishment of the ethanol interfacial molar fraction.  2003 Elsevier Inc. All rights reserved.