Solubility and thermodynamic modeling of quetiapine fumarate in self nanoemulsifying drug delivery system (SNEDDS)

Abstract

Objective: The present study gives emphasis on the development of self-nanoemulsifying drug delivery system (SNEDDS) of poorly water-soluble drug using Apelblat model. Methods: For the development of self-nanoemulsifying drug delivery system (SNEDDS) solubility in surfactant, co-surfactant and in oil phase are considered as an important key to avoid phase separation and precipitation after dilution. The solubility of quetiapine fumarate was determined by the isothermal mechanical shaking method for its individual components in the temperature range from 305.15 to 330.15K was measured. The experimental mole fraction solubility of quetiapine was good correlated with calculated data by using modified Apelblat model. Prepared SNEDDS were evaluated in centrifugation, freeze-thaw cycle study, self-nanoemulsification efficiency test. Physicochemical properties of prepared SNEDDS including particle size, zeta potential, viscosity and refractive index were carried out. Results: The equilibrium saturated and mole fraction solubility of Quetiapine fumarate was found to be high in tween80 than SNEDDS, Labrafac lipophile WL 1349 and capryol 90. Quetiapine fumarate equilibrium saturated solubility, as well as mole fraction solubility, was found to be increased with increase in temperature in SNEDDS as well as in its individual components Prepared SNEDDS was found to be highly stable at centrifugation, heating and cooling cycles and freeze-thaw cycles and shows no sign of precipitation after dilution in water. All physicochemical parameters were observed within specification including droplet size observed as 26.37 nm, polydispersity index 0.0970, zeta potential-14.69 and the refractive index was observed as 1.458 which was nearer to the refractive index of water indicating the isotropic behavior of prepared SNEDDS. Conclusion: The solubility study could be an effective approach for the development of thermodynamically stable SNEDDS formulation of poorly soluble drugs using Apelblat model.