Lipid Solid Dispersions for the Aqueous Solubility and Bioavailability Enhancement of Entacapone

Abstract

The main objective of the present study is to increase the aqueous solubility and in vivo bioavailability of entacapone by preparing the solid dispersion by spray drying. The prepared spray dried dispersions are duly characterized for drug content, particle size distribution, drug morphological conversion in vitro dissolution and in vivo bioavailability. The drug content in the prepared dispersions is between 85.7 and 95.3 % (w/w) of the theoretical values and the mean volume diameter of the particles collected from drying chamber and cyclone are found to be 12.43 and 69.19 μm, respectively. The DSC thermograms have indicated the morphological conversion of entacapone to amorphous form. The saturation solubility for entacapone in the spray dried formulation is 4.6 and 1.8 times higher to the plain drug and spray dried drug, respectively. The dissolution of entacapone in acetate buffer pH 1.2 is 79 % in the solid dispersion formulation whereas it is only 11 % in the plain drug in 1 h. The release of entacapone in all the three pH conditions studied is instantaneous and complete indicating the pH independent release behaviour from the formulation. The formulations have demonstrated the significant improvement of bioavailability (AUC = 54048 ng/h/mL) compared to plain drug suspension (AUC = 9438 ng/h/mL). These results demonstrated the efficacy of solid lipid dispersions for the enhancement of entacapone bioavailability by increasing its aqueous solubility.