title: Development of topical ophthalmic In Situ gel-forming estradiol delivery system intended for the prevention of age-related cataracts.
abstract: The goal of this study was to develop and characterize an ion-activated in situ gel-forming estradiol (E2) solution eye drops intended for the prevention of age-related cataracts. Accordingly, in situ gelling eye drops were made using gellan gum as an ion-activated gel-forming polymer, polysorbate-80 as drug solubilizing agent, mannitol as tonicity agent, and combination of potassium sorbate and edetate disodium dihydrate (EDTA) as preservatives. The formulations were tested for the following characteristics: pH, clarity, osmolality, antimicrobial efficacy, rheological behavior, and in vitro drug release. Stability of the formulation was also monitored for 6 months at multiple storage conditions per ICH Q1A (R2) guidelines. The solution eye drops resulted in an in-situ phase change to gel-state when mixed with simulated tear fluid (STF). The gel structure formation was confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 80% of drug released in 8 hr. The formulations were found to be clear, isotonic with suitable pH and viscoelastic behavior and stable at accelerated and long-term storage conditions for 6 months. In vitro results suggest that the developed formulation is suitable for further investigation in animal models to elucidate the ability of estrogen to prevent and delay cataracts.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America.
authors.forename: Udaya K
authors.initials: UK
authors.lastname: Kotreka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Davis
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, United States of America.
authors.forename: Moji C
authors.identifier: http://orcid.org/0000-0003-3808-3166
authors.initials: MC
authors.lastname: Adeyeye
mesh_terms: D060433:Administration, Ophthalmic; D000375:Aging; D001419:Bacteria / Q000187:drug effects; D001682:Biological Availability; D002386:Cataract / Q000453:epidemiology / Q000517:prevention & control*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D004548:Elasticity; D004958:Estradiol / Q000008:administration & dosage*; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D065346:Lubricant Eye Drops; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D011135:Polysaccharides, Bacterial; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D012212:Rheology; D014783:Viscosity
chemical_list: D005782:Gels; D065346:Lubricant Eye Drops; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; D011310:Preservatives, Pharmaceutical; D004958:Estradiol; C048288:gellan gum