title: Solubility enhancement of miconazole nitrate: binary and ternary mixture approach.
abstract: BACKGROUND
  Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations.
  
  
  OBJECTIVE
  Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach.
  
  
  METHODS
  Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release.
  
  
  RESULTS
  An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2 h from the mixtures of MN and polymers.
  
  
  CONCLUSIONS
  RESULTS revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD.
  
  
  CONCLUSIONS
  Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4 μg/ml to 57640.0 μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.
authors.affiliation: Herbal Medicinal Product Department, Council of Scientific and Industrial Research, Central Institute of Medicinal and Aromatic Plants , Lucknow, Uttar Pradesh , India .
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Rai
authors.forename: Harinath
authors.initials: H
authors.lastname: Dwivedi
authors.forename: Narayan Prasad
authors.initials: NP
authors.lastname: Yadav
authors.forename: Chandan Singh
authors.initials: CS
authors.lastname: Chanotiya
authors.forename: Shubhini A
authors.initials: SA
authors.lastname: Saraf
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065546:Drug Liberation; D007785:Lactose / Q000737:chemistry; D008825:Miconazole / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D011108:Polymers; D047392:beta-Cyclodextrins; D014867:Water; D011092:Polyethylene Glycols; D008825:Miconazole; D007785:Lactose; C031215:betadex
keywords: Binary mixture; inclusion complex; solid dispersion; solvent deposition; ternary mixture