{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:54:36Z","timestamp":1790553276517,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Leo, Mary, and Mary-Ann Hackman Foundation"},{"DOI":"10.13039\/100011102","name":"FP7","doi-asserted-by":"publisher","award":["280761"],"award-info":[{"award-number":["280761"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["14503"],"award-info":[{"award-number":["14503"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2018,7]]},"DOI":"10.1016\/j.ejps.2018.03.034","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T09:57:02Z","timestamp":1522749422000},"page":"83-89","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":144,"special_numbering":"C","title":["Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye"],"prefix":"10.1016","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-5873","authenticated-orcid":false,"given":"Eva","family":"Ramsay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"del Amo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Toropainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unni","family":"Tengvall-Unadike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli-Pekka","family":"Ranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6064-3102","authenticated-orcid":false,"given":"Arto","family":"Urtti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Ruponen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejps.2018.03.034_bb0005","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s13346-015-0275-6","article-title":"In vitro and ex vivo corneal penetration and absorption models","author":"Agarwal","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0010","first-page":"584","article-title":"Importance of the noncorneal absorption route in topical ophthalmic drug delivery","volume":"26","author":"Ahmed","year":"1985","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0015","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0378-5173(87)90092-5","article-title":"Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption","volume":"38","author":"Ahmed","year":"1987","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0020","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/jps.2600760802","article-title":"Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea","volume":"76","author":"Ahmed","year":"1987","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0025","first-page":"2581","article-title":"pH and drug ionization affects ocular pressure lowering of topical carbonic anhydrase inhibitors","volume":"34","author":"Brechue","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0030","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1089\/jop.1987.3.159","article-title":"Nasal and conjunctival contributions to the systemic absorption of topical timolol in the pigmented rabbit: implications in the design of strategies to maximize the ratio of ocular to systemic absorption","volume":"3","author":"Chang","year":"1987","journal-title":"J. Ocul. Pharmacol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0035","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0014-4835(88)80093-9","article-title":"Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol","volume":"46","author":"Chang","year":"1988","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0040","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3109\/02713689008997579","article-title":"Corneal and conjunctival\/scleral penetration of p-aminoclonidine, AGN 190342, and clonidine in rabbit eyes","volume":"9","author":"Chien","year":"1990","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0045","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/0002-9394(74)90541-8","article-title":"Corneal permeation of topical pilocarpine nitrate in the rabbit","volume":"77","author":"Chrai","year":"1974","journal-title":"Am J. Ophthalmol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0050","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1002\/jps.2600620712","article-title":"Lacrimal and instilled fluid dynamics in rabbit eyes","volume":"62","author":"Chrai","year":"1973","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0055","first-page":"149","article-title":"Influence of tonicity and pH on lacrimation and ocular drug bioavailability","volume":"32","author":"Conrad","year":"1978","journal-title":"J. Parenter. Drug Assoc."},{"key":"10.1016\/j.ejps.2018.03.034_bb0060","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S1350-9462(02)00038-1","article-title":"Regulation of mucin and fluid secretion by conjunctival epithelial cells","volume":"21","author":"Dartt","year":"2002","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0065","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1007\/s11095-016-1993-2","article-title":"General pharmacokinetic model for topically administered ocular drug dosage forms","volume":"33","author":"Deng","year":"2016","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0070","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0002-9394(14)77735-9","article-title":"Penetration routes of topically applied eye medications","volume":"85","author":"Doane","year":"1978","journal-title":"Am J. Ophthalmol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0075","first-page":"2251","article-title":"A model to predict aqueous humor and plasma pharmacokinetics of ocularly applied drugs","volume":"34","author":"Grass","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0080","first-page":"627","article-title":"Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera","volume":"38","author":"H\u00e4m\u00e4l\u00e4inen","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0085","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/jps.2600670507","article-title":"Preliminary pharmacokinetic model of pilocarpine uptake and distribution in the eye","volume":"67","author":"Himmelstein","year":"1978","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0090","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/jps.2600721108","article-title":"Corneal penetration behavior of \u03b2-blocking agents II: assessment of barrier contributions","volume":"72","author":"Huang","year":"1983","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0095","first-page":"684","article-title":"Paracellular permeability of corneal and conjunctival epithelia","volume":"30","author":"Huang","year":"1989","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2003.09.016","article-title":"Vesicular systems in ocular drug delivery: an overview","author":"Kaur","year":"2004","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0105","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1007\/s11095-010-0132-8","article-title":"Prediction of the corneal permeability of drug-like compounds","volume":"27","author":"Kidron","year":"2010","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0110","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0014-4835(75)90099-8","article-title":"Pilocarpine levels in the eyes of rabbits following topical application","volume":"21","author":"Lazare","year":"1975","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0115","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jps.2600680606","article-title":"Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits","volume":"68","author":"Lee","year":"1979","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0120","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/jop.1986.2.67","article-title":"Review: topical ocular drug delivery: recent developments and future challenges","volume":"2","author":"Lee","year":"1986","journal-title":"J. Ocul. Pharmacol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0125","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0378-5173(92)90308-O","article-title":"The effect of drug charge type and charge density on corneal transport","volume":"88","author":"Liaw","year":"1992","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0130","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1021\/jm051231p","article-title":"Computational prediction of oral drug absorption based on absorption rate constants in humans","volume":"49","author":"Linnankoski","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejps.2018.03.034_bb0135","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejps.2012.05.007","article-title":"Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes","volume":"47","author":"Loch","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0140","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/jps.2600680411","article-title":"Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye","volume":"68","author":"Makoid","year":"1979","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0145","series-title":"Handbook of Experimental Pharmacology\/Pharmacology of the Eye","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-642-69222-2_2","article-title":"Ocular pharmacokinetics","author":"Maurice","year":"1984"},{"key":"10.1016\/j.ejps.2018.03.034_bb0150","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/BF01070899","article-title":"A physiologically based pharmacokinetic model for the intraocular distribution of pilocarpine in rabbits","volume":"9","author":"Miller","year":"1981","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0155","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/0002-9394(86)90532-5","article-title":"Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution, 1978\u20131985","volume":"102","author":"Nelson","year":"1986","journal-title":"Am J. Ophthalmol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0160","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/jps.24231","article-title":"Development of a convenient ex vivo model for the study of the transcorneal permeation of drugs: histological and permeability evaluation","volume":"104","author":"Pescina","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0165","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1021\/js9802594","article-title":"Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye","volume":"87","author":"Prausnitz","year":"1998","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0170","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.xphs.2017.04.061","article-title":"Impact of chemical structure on conjunctival drug permeability: adopting porcine conjunctiva and cassette dosing for construction of in silico model","volume":"106","author":"Ramsay","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0175","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jconrel.2010.08.028","article-title":"Barrier analysis of periocular drug delivery to the posterior segment","volume":"148","author":"Ranta","year":"2010","journal-title":"J. Control. Release"},{"key":"10.1016\/j.ejps.2018.03.034_bb0180","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/jps.2600721108","article-title":"Corneal penetration behavior of \u03b2-blocking agents I: physicochemical factors","volume":"72","author":"Schoenwald","year":"1983","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0185","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3109\/02713683.2015.1050738","article-title":"Hydrogel ring for topical drug delivery to the ocular posterior segment","volume":"41","author":"Shikamura","year":"2016","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0190","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jps.2600730219","article-title":"Quantitative evaluation of topically applied pilocarpine in the precorneal area","volume":"73","author":"Thombre","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.03.034_bb0195","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.addr.2006.07.027","article-title":"Challenges and obstacles of ocular pharmacokinetics and drug delivery","volume":"58","author":"Urtti","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejps.2018.03.034_bb0200","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0039-6257(93)90141-S","article-title":"Minimizing systemic absorption of topically administered ophthalmic drugs","volume":"37","author":"Urtti","year":"1993","journal-title":"Surv. Ophthalmol."},{"key":"10.1016\/j.ejps.2018.03.034_bb0205","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0378-5173(85)90005-5","article-title":"Systemic absorption of ocular pilocarpine is modified by polymer matrices","volume":"23","author":"Urtti","year":"1985","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0210","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0378-5173(90)90215-P","article-title":"Controlled drug delivery devices for experimental ocular studies with timolol 2. Ocular and systemic absorption in rabbits","volume":"61","author":"Urtti","year":"1990","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.03.034_bb0215","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1023\/A:1018938310628","article-title":"Controlled ocular timolol delivery: systemic absorption and intraocular pressure effects in humans","volume":"11","author":"Urtti","year":"1994","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0220","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3109\/02713689109001766","article-title":"Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration","volume":"10","author":"Wang","year":"1991","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0225","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3109\/02713688809031801","article-title":"Comparison of conjunctival and corneal surface areas in rabbit and human","volume":"7","author":"Watsky","year":"1988","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.ejps.2018.03.034_bb0230","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1021\/jm9810102","article-title":"Correlation of human jejunal permeability (in vivo) of drugs with experimentally and theoretically derived parameters. A multivariate data analysis approach","volume":"41","author":"Winiwarter","year":"1998","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejps.2018.03.034_bb0235","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2004.07.001","article-title":"Model of transient drug diffusion across cornea","volume":"99","author":"Zhang","year":"2004","journal-title":"J. Control. Release"}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718301556?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718301556?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:22:01Z","timestamp":1534951321000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098718301556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":47,"alternative-id":["S0928098718301556"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2018.03.034","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2018.03.034","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}