Abstract
Context: Colchicine (CLC) causes cell death by destabilizing the tubulin unit. However, it ionizes at physiological pH resultant low bioavailability and therapeutic efficacy.
Objectives: We have attempted to augment the bioavailability of CLC by fabricating the inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD).
Materials and 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, 1H nuclear magnetic resonance (1H 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.
Results and discussion: Our phase-solubility data indicated the formation of a stable complex with Kc ~0.31 mM−1 at pH 7.4. 1H NMR ascertains that NHCOCH3 moiety of CLC enters in the HP-β-CD cavity and deshielded the H-3 and H-5 protons. ROESY also correlates the Hf and Hg of CLC with H-3 and H-5 protons of HP-β-CD and indicates that Hf and Hg 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.
Conclusion: CLC-HP-β-CD inclusion complex may potentially be used as a viable formulation of CLC.
Acknowledgements
We thank Gangwal Chemical Private Limited, Mumbai, India for the gift sample of HP-β-CD and Dr. Devender Kumar, Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, India for their kind help in analyzing the NMR spectra.
Declaration of interest
There are no conflicts of interest.