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

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.