Cyclodextrin-mediated enhancement of riboflavin solubility and corneal permeability

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.