Preparation of curcumin-hydroxypropyl-β-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug.

The curcumin (CUR)-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complex (CUR-HP-beta-CD) was prepared to erase its therapeutic restrictions of poor aqueous solubility and low oral bioavailability. CUR-HP-beta-CD was prepared by a simple procedure of water-ethanol cosolvent incubation-lyophilization which may be suitable for scale up production, and characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), phase solubility method and dissolution study; the in vitro cytotoxicity was assayed by MTT, whereas the in vivo pharmacokinetics was tested by HPLC in rats receiving formulations via intravenous and oral administration, respectively. CUR was successfully encapsulated in HP-beta-CD with a loading capacity of about 1:7 of CUR to HP-beta-CD mole ratio, which remarkably enhanced drug water solubility and maintained well the antitumour activity of CUR. The CUR-HP-beta-CD and free CUR have a similar pharmacokinetic behaviour in rats after intravenous administration; however, the oral bioavailability of CUR was enhanced to 2.77-fold by the HP-beta-CD. The CUR-HP-beta-CD can be successfully prepared by a simple method, which may be feasible for industrial scaling up, to remarkably increase drug water solubility and oral bioavailability while maintaining its bioactivity and may be a promising therapeutic preparation.