Docetaxel/dimethyl-β-cyclodextrin inclusion complexes: preparation, in vitro evaluation and physicochemical characterization

Abstract

Despite the development in novel drug delivery techniques and synthesis of multifunctional excipients, oral delivery of hydrophobic drug like docetaxel (DTX) is still challenging. The present work investigates the inclusion complexation of DTX, and dimethyl-β-cyclodextrin (DM-β-CD) to improve the solubility, dissolution and permeability of the drug. Amongst the native and modified β-cyclodextrins, DM-β-CD showed the highest solubility of DTX. Solid binary inclusion complex (IC) of DTX with DM-β-CD was prepared by solvent evaporation technique and thoroughly characterized for solubility, dissolution, permeability, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (1H NMR). The aqueous solubility and in vitro dissolution rate of DTX/DM-β-CD IC were markedly increased by 76.04- and 3.55-fold compared to free DTX powder. The permeability of DTX/DM-β-CD IC showed similar absorptive permeability but decreased efflux from the absorbed DTX, compared to pure DTX. Further, physicochemical studies of IC revealed the change of crystalline state DTX to its amorphous form. Moreover, FT-IR and 1H NMR results indicate the formation of true inclusion complex between DTX and DM-β-CD at 1:1 molar ratio. Collectively, solid inclusion complexes prepared by spray drying method can be an effective strategy to enhance the biopharmaceutical performance of a highly hydrophobic drug DTX.