Chemical factors affecting cucurbit[n]uril formulation into ocular dosage forms: excipient binding, solubility, corneal permeability and antibiotic encapsulation

Abstract

The chemical factors affecting cucurbit[n]uril (CB[n], n = 6, 7 or 8) formulation into ocular dosage forms suitable for delivery to the eye were examined. The poor solubility of CB[8] excludes its formulation even with the use of NaCl to achieve isotonicity, but despite the poor solubility of CB[6] in pure water, it can be dissolved in saline up to concentrations of 2.4% w/v. As both CB[7] and CB[8] are able to bind to the antimicrobial preservatives – benzalkonium chloride and chlorhexidine, neither of these excipients can be co-formulated into eye drops. Where CB[7] is used, the only suitable preservative is sodium metabisulfite. There are no incompatibilities between CB[6] and any of the three preservatives. Ocular penetration of fluorescently tagged CB[7] was examined using bovine corneas and Franz cells. The poor lipophilicity of CB[7] means it does not penetrate through the cornea, and as such, it is unsuitable for intraocular delivery. The ability of CB[7] to form host–guest complexes with the antibiotics ciprofloxacin and chloramphenicol may mean that ocular dosage forms containing cucurbiturils may still have application in treating conjunctivitis.