title: Inclusion complex of colchicine in hydroxypropyl-β-cyclodextrin tenders better solubility and improved pharmacokinetics.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Hindu College of Pharmacy, Sonepat, Haryana, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Chauhan
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kaushik
authors.forename: Satish
authors.initials: S
authors.lastname: Sardana
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003078:Colchicine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D011522:Protons; D011897:Random Allocation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D011522:Protons; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003078:Colchicine