title: Water-soluble Complex of Curcumin with Cyclodextrins: Enhanced Physical Properties For Ocular Drug Delivery.
abstract: BACKGROUND
  Curcumin, a natural hydrophobic polyphenol, has been reported to have diverse pharmacological activities. Previous studies have evaluated its efficacy using both oral and transdermal dosage forms. However, two major obstacles-poor aqueous solubility and low stability-severely limited its pharmaceutical use.
  
  
  OBJECTIVE
  The main objective of this study was to prepare curcumin eye drops that provided sustained release to allow for once daily application in retinitis pigmentosa.
  
  
  METHODS
  To achieve our goal, curcumin was complexed with β -cyclodextrin and hydroxypropyl-β- cyclodextrin in two molar ratios (1:1 and 1:2) using co-solvent, co-solvent with sonication and freezedrying filtration methods. A total of 12 complexes were prepared, then characterized using differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, solubility assessment and in vitro release studies.
  
  
  RESULTS
  An improvement in curcumin aqueous solubility relative to pure curcumin was achieved for all 12 complexes. However, the freeze-drying filtration method was superior to all other methods because it produced highly water-soluble drug-CD complexes. Based on our stability analyses, pH 6.8 phosphate buffer containing 1% Tween 80 was selected as the release medium for in vitro release studies because curcumin exhibited high stability in this medium. Our F11 formulation provided sustained release of the drug for more than 96 h with a maximum amount released of drug (21.77±0.26 μg/ml). Our in vitro release data also showed that release of drug from curcumin-CDs inclusion complexes followed a Higuchi non-Fickian diffusion mechanism.
  
  
  CONCLUSIONS
  Based on these results, F11 was formulated as eye drops, which provide a promising once daily novel topical delivery of this naturally derived phytochemical.
authors: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors: Doaa Nabih
authors: DN
authors: Maria
authors: Department of Physics and Materials Science, University of Memphis, Memphis, TN, United States.
authors: Sanjay R
authors: SR
authors: Mishra
authors: Department of Physics and Materials Science, University of Memphis, Memphis, TN, United States.
authors: Lijia
authors: L
authors: Wang
authors: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors: Abd-Elgawad Helmy
authors: AH
authors: Abd-Elgawad
authors: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors: Osama Abd-Elazeem
authors: OA
authors: Soliman
authors: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors: Marwa Salah
authors: MS
authors: El-Dahan
authors: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Monica M
authors: MM
authors: Jablonski
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005123:Eye / Q000187:drug effects*; D005612:Freeze Drying / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009883:Ophthalmic Solutions / Q000737:chemistry*; D012995:Solubility / Q000187:drug effects; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D009883:Ophthalmic Solutions; D012997:Solvents; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003474:Curcumin; C031215:betadex
keywords: Anti-inflammatory; curcumin; cyclodextrin; freeze-drying filtration; inclusion complexes; β-cyclodextrin