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

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-beta-cyclodextrin (HP-beta-CD). Materials and methods: CLC-HP-beta-CD inclusion complex was prepared and evaluated with Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy, H-1 nuclear magnetic resonance (H-1 NMR) spectroscopy and rotating frame overhauser enhancement spectroscopy (ROESY). Oral bioavailability of CLC-HP-beta-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 K-c similar to 0.31 mM(-1) at pH 7.4. H-1 NMR ascertains that NHCOCH 3 moiety of CLC enters in the HP-beta-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-beta-CD and indicates that H-f and H-g protons of CLC are present either as cis and/or trans form in CLC-HP-beta-CD inclusion complex. Pharmacokinetic studies showed a 1.82-fold increase in absolute bioavailability of CLC upon complexation. Conclusion: CLC-HP-beta-CD inclusion complex may potentially be used as a viable formulation of CLC.