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

Abstract

The curcumin (CUR)-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex (CUR-HP-β-CD) was prepared to erase its therapeutic restrictions of poor aqueous solubility and low oral bioavailability. CUR-HP-β-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-β-CD with a loading capacity of about 1:7 of CUR to HP-β-CD mole ratio, which remarkably enhanced drug water solubility and maintained well the antitumour activity of CUR. The CUR-HP-β-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-β-CD. The CUR-HP-β-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.

Keywords:

• Herbal component
• anticancer
• drug carrier
• oral administration
• freeze-drying
• cytotoxicity
• pharmacokinetics

Acknowledgements

The authors thanked Zibin Gao from Hebei University of Science & Technology and Yiguang Jin from Military Medicinal Science Academy for kindly providing valuable help in experiments.

Disclosure of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported under Grant KJ2016SD28 and gxfxZD2016045 (provided by the Department of Education of Anhui Province for College Natural Science Research Project and for Elite Teacher Study Abroad as a Visiting Scholar, respectively, to TW); and under Grant 1708085QH195 (provided by the Department of Science and Technology of Anhui Province for Youth Natural Science Research Project to NW); and under Grant 81703449 (provided by the National Natural Science Foundation of China for youth scientist to NW).