title: Evaluation of physicochemical properties, skin permeation and accumulation profiles of ketorolac fatty ester prodrugs.
abstract: The purpose of this study was to evaluate the physicochemical properties, skin permeation and accumulation profiles of model lipophilic ketorolac fatty ester (esters) prodrugs. Ketorolac linoleate (C18:2), oleate (C18:1) and stearate (C18:0) were evaluated for their solubility, capacity factor, enzymatic hydrolysis, chemical stability, and skin permeation and accumulation profiles using the combination of common permeation enhancing techniques such as the use of supersaturated solution of permeants in the enhancer vehicle, lipophilic receptor solution, enhancer pretreatment of skins, removal of stratum corneum and delipidization of skins etc. Esters were highly lipophilic, chemically stable for the duration of observation, enzymatically unstable in hairless mouse skin/liver homogenates and plasma, and impermeable into the receptor solution. Absence of skin permeation, relative enzymatic stability during permeation and chemical stability of these esters could delineate preliminary possibilities for designing safer topical agents without systemic absorption.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
authors.forename: Krishna Hari
authors.initials: KH
authors.lastname: Bhandari
authors.forename: Madhuri
authors.initials: M
authors.lastname: Newa
authors.forename: Sung Ii
authors.initials: SI
authors.lastname: Yoon
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Jang
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Bong Kyo
authors.initials: BK
authors.lastname: Yoo
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.forename: Jae Hwi
authors.initials: JH
authors.lastname: Lee
authors.forename: Dae Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Hang Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004952:Esters / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D020910:Ketorolac / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D015394:Molecular Structure; D008970:Molecular Weight; D010539:Permeability; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012995:Solubility; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D011355:Prodrugs; D020910:Ketorolac