In vitro nimesulide absorption from different formulations.

In light of improving the bioavailability of poorly water-soluble drugs, this work focused on the comparison among different nimesulide formulations resorting to in vitro absorption experiments through everted rat intestine. The performance of a nimesulide ethanol-triacetin solution, an activated system made up by cogrinding nimesulide/polyvinylpyrrolidone and simple solid nimesulide were compared with that of a reference nimesulide solution. Although ethanol-triacetin solution showed a better performance than the solid nimesulide because wettability problems connected with nimesulide were completely zeroed, the activated system showed a better performance than the reference solution one. This was due to the fact that the activated system allowed to overcome both the wettability and solubility problems connected with nimesulide. Moreover, as proved by intestinal pictures taken before and after permeation experiments, we observed the adhesion of polymeric particles to intestinal villi, this giving origin to a thin layer, surrounding the intestine, characterized by a nimesulide concentration higher than that in the release environment bulk. A proper mathematical model, based on Fick's second law, was developed to model drug absorption in the case of solution and activated system. In this manner, we could calculate nimesulide permeability through the intestinal wall, and we could better define the nature of the above-mentioned thin layer surrounding the intestine. Finally, the mathematical model was used to verify the theoretical correctness of the widely employed technique consisting in data correction for dilution when sample withdrawal and replacement were needed to measure drug concentration in the receiver environment.

Characterization of a quaternary liquid system improving the bioavailability 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 three-component 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.