Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance.
To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Marija N
MN
Todosijević
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Miroslav M
MM
Savić
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Bojan B
BB
Batinić
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Bojan D
BD
Marković
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
Mirjana
M
Gašperlin
ICTM - Institute of Microelectronic Technologies, University of Belgrade, 11000 Belgrade, Serbia.
Danijela V
DV
Ranđelović
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Milica Ž
MŽ
Lukić
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia. Electronic address: snexs@pharmacy.bg.ac.rs.
Snežana D
SD
Savić
D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D002152:Calorimetry, Differential Scanning; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D005260:Female; D006801:Humans; D007509:Irritants / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D012995:Solubility; D013395:Sucrose / Q000737:chemistry; D013501:Surface-Active Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D004655:Emulsions; D007509:Irritants; D013501:Surface-Active Agents; D004008:Diclofenac; D013395:Sucrose; C056498:aceclofenac
Aceclofenac; Bicontinuous microemulsion; Pharmacokinetics; Skin irritation potential; Sucrose ester; Tape stripping