Inclusion complex of colchicine in hydroxypropyl-β-cyclodextrin tenders better solubility and improved pharmacokinetics.

BACKGROUND

Colchicine (CLC) causes cell death by destabilizing the tubulin unit. However, it ionizes at physiological pH resultant low bioavailability and therapeutic efficacy.

OBJECTIVE

We have attempted to augment the bioavailability of CLC by fabricating the inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD).

METHODS

CLC-HP-β-CD inclusion complex was prepared and evaluated with Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy and rotating frame overhauser enhancement spectroscopy (ROESY). Oral bioavailability of CLC-HP-β-CD inclusion complex was analyzed using high performance liquid chromatography method.

CONCLUSIONS

Our phase-solubility data indicated the formation of a stable complex with K(c) ~0.31 mM(-1) at pH 7.4. (1)H NMR ascertains that NHCOCH(3) moiety of CLC enters in the HP-β-CD cavity and deshielded the H-3 and H-5 protons. ROESY also correlates the H(f) and H(g) of CLC with H-3 and H-5 protons of HP-β-CD and indicates that H(f) and H(g) protons of CLC are present either as cis and/or trans form in CLC-HP-β-CD inclusion complex. Pharmacokinetic studies showed a 1.82-fold increase in absolute bioavailability of CLC upon complexation.

CONCLUSIONS

CLC-HP-β-CD inclusion complex may potentially be used as a viable formulation of CLC.