Characterization, in vivo and in vitro evaluation of solid dispersion of curcumin containing D-α-Tocopheryl polyethylene glycol 1000 succinate and mannitol

Abstract

The aim of this study was to prepare a solid dispersion formulation of curcumin t enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared wit D---Tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporatio and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin soli dispersion markedly improved compared with those of curcumin powder and a physical mixture o curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersio formulation within 10 min. After administering the formulation orally to rats, higher plasm concentrations of curcumin were observed, with increases in the maximum plasma concentratio (Cmax) and area under the plasma concentration-Time curve (AUC) of 86-And 65-fold, respectively compared with those of curcumin powder. The solid dispersion formulation effectively increase intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferativ effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumi powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effec of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibitio of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersio formulation of curcumin with TPGS and mannitol could be a promising option for enhancin the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate cell permeability, and P-gp modulation.