Thermodynamic modeling for solubility prediction of indomethacin in self-nanoemulsifying drug delivery system (SNEDDS) and its individual components.

Abstract For the development of an effective self-nanoemulsifying drug delivery system (SNEDDS) of poorly soluble drugs, the knowledge of the solubility in its oil phase and SNEDDS are one of the most important factors to avoid possibility of drug to get phase separated or precipitated upon dilution with gastrointestinal fluids. With this background, this study was undertaken to determine the equilibrium saturated solubility as well as mole fraction solubility of indomethacin in prepared SNEDDS and its individual components at the temperature range of 295.15 to 320.15 K. The equilibrium solubilities of indomethacin in each sample matrices were determined by an isothermal mechanical shaking method and the resulting data was analyzed by regression analysis. The experimental mole fraction solubility data of indomethacin at various temperatures was well correlated with the modified Apelblat model. The equilibrium saturated solubility as well as mole fraction solubility of indomethacin was found to be increased with increase in temperature in SNEDDS as well as in its individual components. The mole fraction solubility of indomethacin was found to be significantly higher in Tween-80 than SNEDDS, Labrafil-M1944CS and Transcutol-HP. These preliminary studies on solubility could be a useful tool for the development of an efficient and thermodynamically stable SNEDDS formulation of various poorly soluble drugs to enhance their solubility/dissolution and oral bioavailability.