title: W/O microemulsions for ocular delivery: evaluation of ocular irritation and precorneal retention.
abstract: Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were formulated using Crodamol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as cosurfactant and water. The hypothesis that phase-transition of ME to LC may be induced by tears and serve to prolong precorneal retention was tested. The ocular irritation potential of components and formulations was assessed using a modified hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of selected formulations was investigated in rabbit eye using gamma scintigraphy. Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant. However, all other cosurfactants investigated were irritant and their irritation was dependent on their carbon chain length. A w/o ME formulated without cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was used as the aqueous phase. Precorneal clearance studies revealed that the retention of colloidal and coarse dispersed systems was significantly greater than an aqueous solution with no significant difference between ME systems (containing 5% and 10% water) as well as o/w emulsion containing 85% water. Conversely, a LC system formulated without cosurfactant displayed a significantly greater retention compared to other formulations.
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Room 40017, Lower Ground Floor, Building 504, Cnr Boyle Crescent and Glasgow Terrace, Grafton, Private Bag 92019, Auckland 1100, New Zealand. r.alany@auckland.ac.nz
authors.forename: R G
authors.initials: RG
authors.lastname: Alany
authors.forename: T
authors.initials: T
authors.lastname: Rades
authors.forename: J
authors.initials: J
authors.lastname: Nicoll
authors.forename: I G
authors.initials: IG
authors.lastname: Tucker
authors.forename: N M
authors.initials: NM
authors.lastname: Davies
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003315:Cornea / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004655:Emulsions / Q000737:chemistry*; D005123:Eye / Q000378:metabolism*; D005128:Eye Diseases / Q000139:chemically induced / Q000378:metabolism; D066298:In Vitro Techniques; D007509:Irritants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D050866:Liquid Crystals / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D011877:Radionuclide Imaging / Q000379:methods; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D007509:Irritants; D009829:Oleic Acids; D011108:Polymers; C422409:liquid crystal polymer; D014867:Water; C033180:ethyl oleate