DEXAMETHASONE-CYCLODEXTRIN-POLYMER CO-COMPLEXES IN AQUEOUS EYE DROPS - AQUEOUS-HUMOR PHARMACOKINETICS IN HUMANS

Purpose. To test an aqueous eye drop solution containing a high concen tration of dexamethasone in a cyclodextrin-based drug delivery system. This system increases both drug solubility in aqueous eye drops and d rug permeability into the eye, through drug-cyclodextrin-polymer co-co mplexes. Methods. 2-hydroxypropyl-beta-cyclodextrin is a water-soluble oligosaccharide that can be used to dissolve lipophilic drugs, such a s dexamethasone, in aqueous solutions. Co-complexation with a polymer further increases the solubility and increases drug permeability throu gh biologic membranes. Eye drops containing dexamethasone (0.32% and 0 .67%), 2-hydroxypropyl-beta-cyclodextrin, and polymer were given to pa tients before cataract surgery, and the resultant dexamethasone concen tration was measured from aqueous humor samples. Results. The dexameth asone-cyclodextrin drops give a significantly higher concentration of dexamethasone in aqueous humor than dexamethasone alcohol 0.1% (Maxide x). Heating of the dexamethasone-cyclodextrin-polymer co-complexes app ears to enhance the permeability of the drug into the eye. Conclusions . The cyclodextrin-based drug delivery system enhances both the solubi lity of dexamethasone in aqueous eye drops and the permeability of the drug into the human eye. Dexamethasone concentration levels in the hu man aqueous humor exceed those reported with currently available stero id eye drops.