Evaluation of physicochemical properties, skin permeation and accumulation profiles of ketorolac fatty ester prodrugs.
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.
Bhandari
Krishna Hari
KH
College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
Newa
Madhuri
M
Yoon
Sung Ii
SI
Kim
Jung Sun
JS
Jang
Ki Young
KY
Kim
Jung-Ae
JA
Yoo
Bong Kyo
BK
Woo
Jong Soo
JS
Lee
Jae Hwi
JH
Kim
Dae Duk
DD
Choi
Hang Gon
HG
Yong
Chul Soon
CS
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D011355:Prodrugs; D020910:Ketorolac