title: Cyclodextrin-mediated enhancement of riboflavin solubility and corneal permeability.
abstract: Cyclodextrins are water-soluble cyclic oligosaccharides consisting of six, seven, and eight α-(1,4)-linked glucopyranose subunits. This study reports the use of different cyclodextrins in eye drop formulations to improve the aqueous solubility and corneal permeability of riboflavin. Riboflavin is a poorly soluble drug with a solubility up to 0.08 mg mL(-1) in deionized water. It is used as a drug topically administered to the eye to mediate UV-induced corneal cross-linking in the treatment of keratoconus. Aqueous solutions of β-cyclodextrin (10-30 mg mL(-1)) can enhance the solubility of riboflavin up to 0.12-0.19 mg mL(-1), whereas the higher concentration of α-cyclodextrin (100 mg mL(-1)) achieved a lower level of enhancement of 0.11 mg mL(-1). The other oligosaccharides were found to be inefficient for this purpose. In vitro diffusion experiments performed with fresh and cryopreserved bovine cornea have demonstrated that β-cyclodextrin enhances riboflavin permeability. The mechanism of this enhancement was examined through microscopic histological analysis of the cornea and is discussed in this paper.
authors.affiliation: School of Pharmacy, University of Reading , Whiteknights, P.O. Box 224, Reading, RG6 6AD, United Kingdom.
authors.forename: Peter W J
authors.initials: PW
authors.lastname: Morrison
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
mesh_terms: D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D010539:Permeability / Q000187:drug effects; D012256:Riboflavin / Q000737:chemistry*; D012995:Solubility / Q000187:drug effects
chemical_list: D003505:Cyclodextrins; D012256:Riboflavin