title: Cyclosporin nanosphere formulation for ophthalmic administration.
abstract: Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye disease, and is available commercially as ophthalmic emulsion formulation (RESTASIS(®)). For increasing efficacy, and for reducing local toxicity including irritation to eyes, CsA nanosphere (CsA-NS) formulation was prepared and evaluated, in this work. CsA-NS formulation was prepared in a pre-concentrate form, which is a homogeneous solution of a CsA in a mixture of surfactants, lipids and solvents and provides nanosphere dispersion when added to aqueous medium. CsA-NS formulation was characterized and adjusted for particle size, pH, and osmolarity, suitable for ophthalmic administration. Thereafter, CsA-NS formulation was evaluated for parameters like irritation to eyes and penetrability of CsA in the rabbit eyes. Results obtained demonstrated that proposed CsA-NS formulation causes less irritation in rabbit eyes, with nearly same CsA penetration in the rabbit eyes in comparison to marketed emulsion formulation.
authors.affiliation: Institute of Drug Research, School of Pharmacy-Faculty of Medicine, Center for Nanoscience and Nanotechnology and The Alex Grass Center for Drug Design and Synthesis, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Wahid
authors.initials: W
authors.lastname: Khan
authors.forename: Yanir H
authors.initials: YH
authors.lastname: Aldouby
authors.forename: Avi
authors.initials: A
authors.lastname: Avramoff
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry; D005123:Eye / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry; D006601:Hexoses / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D011817:Rabbits; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D006601:Hexoses; D054709:Lecithins; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D012997:Solvents; D013501:Surface-Active Agents; D014280:Triglycerides; C018665:sorbitan monooleate; D019946:Propylene Glycol; C004565:trilaurin; D016572:Cyclosporine; D005990:Glycerol