title: Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye.
abstract: It is generally believed that it is virtually impossible to obtain therapeutic drug concentrations in the posterior segment of the eye after topical application of aqueous, low viscosity eye drops. Thus, intravitreal drug injections and drug implants are currently used to treat diseases in the posterior segment such as macular edema. Here it is described how, through proper analysis of the drug permeation barriers and application of well-known pharmaceutical excipients, aqueous eye drops are designed that can deliver lipophilic drugs to the posterior segment as well as how such eye drops can maintain high drug concentrations in the anterior segment. Through stepwise optimization, eye drops containing solid drug/cyclodextrin complex microparticles with a mean diameter of 2-4μm, dissolved drug/cyclodextrin complex nanoparticles and dissolved drug molecules in an aqueous eye drop media of low viscosity were designed. After administration of the eye drops the microparticles slowly dissolved and maintained close to saturated drug concentrations in the aqueous tear fluid for several hours. Studies in rabbits and clinical evaluations in humans, using dorzolamide and dexamethasone as sample drugs, show that the eye drops deliver significant amounts of drugs to both the posterior segment and anterior segment of the eye. Clinical studies indicate that the eye drops can replace intravitreal injections and implants that are currently used to treat ophthalmic diseases and decrease frequency of drug administration, both of which can improve patient compliance.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland. Electronic address: thorstlo@hi.is.
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, National University Hospital, Eiríksgata 37, IS-101 Reykjavík, Iceland.
authors.forename: Einar
authors.initials: E
authors.lastname: Stefánsson
mesh_terms: D060433:Administration, Ophthalmic; D000287:Administration, Topical; D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006801:Humans; D009883:Ophthalmic Solutions / Q000008:administration & dosage*; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D003907:Dexamethasone; C062765:dorzolamide
keywords: Aggregates; Cyclodextrin; Eye drops; Microparticles; Nanoparticles; Permeation