Kinetics and Mechanism of Diazepam Release from Solid Dispersions

Abstract

According to the biopharmaceutics classification system, diazepam belongs to the class II drugs. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. The aim of the present study was preparation of diazepam solid dispersions using various carriers like polyethylene glycol 2000, polyethylene glycol 4000 and polyvinylpyrrolidone K30, estimation of solubility and dissolution rate of prepared diazepam solid dispersions and comparison of these data to that of pure diazepam. The solid dispersions were prepared by solvent evaporation method. Phosphate buffer pH 6.8 was used as dissolution medium. Solid dispersions of diazepam with polymers resulted in increased solubility and dissolution rate of diazepam (highest with polyvinylpyrrolidone K30). The rate release kinetics of diazepam from the solid dispersions followed Hixson-Crowell cube root law. The correlation coefficient (r²) values of the Hixson-Crowell’s cube root model were slightly higher (0.9665 to 0.9977) when compared to the zero and first order release model. The high values of regression coefficients suggested that all formulations followed Korsmeyer-Peppas model of release kinetics. The low values of the release exponent (< 0.45) indicated that the mechanism of diazepam release from all the formulations could be described as a Fickian diffusion mechanism.