Effect of counter-ions and penetration enhancers on the skin permeation of flurbiprofen

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 4; pp. 1826 - 1837
• Main Authors: Ma, Xu, Fang, Liang, Guo, Jianpeng, Zhao, Nanxi, He, Zhonggui
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.04.2010; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: 1H-NMR; Amines - pharmacology; Animals; Biological and medical sciences; Ethanol - pharmacology; flurbiprofen; Flurbiprofen - pharmacokinetics; General pharmacology; HPLC; in vitro; ion-pairing; Ions - pharmacology; Magnetic Resonance Spectroscopy; Male; Medical sciences; organic amine; penetration enhancer; percutaneous absorption; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propylene Glycol - pharmacology; Rats; Rats, Wistar; Skin - drug effects; Skin - metabolism; Skin Absorption - drug effects; solubility; transdermal; penetration enhancer; percutaneous absorption; flurbiprofen; 1H-NMR; transdermal; in vitro; solubility; organic amine; ion-pairing; HPLC; Prostaglandin-endoperoxide synthase; HPLC chromatography; Percutaneous route; Absorption; Amine; Arylpropionic acid derivatives; Pairing; Flurbiprofen; H-NMR; Pharmaceutical technology; Enzyme; Permeation; Solubility; Enzyme inhibitor; Ions; In vitro; Non steroidal antiinflammatory agent; Skin; Absorption enhancer; Oxidoreductases; Pharmacokinetics; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21953

The aim of this work was to investigate the percutaneous absorption of flurbiprofen (FP) using counter-ions as enhancers as well as to compare their enhancing activity with penetration enhancers in vitro. The in vitro permeation studies of FP were performed in isopropyl myristate (IPM) solution by two-chamber diffusion cells, using rat abdominal skin as a model. Among the penetration enhancers examined, including the cosolvents of propylene glycol and ethanol (EtOH), oleic acid, menthol, laurocapram, sorbitan monooleate, and N-methyl-2-pyrrolidone (NMP), 10% (w/w) EtOH and NMP exhibited the most potent solubilization and enhancing effects of FP from IPM, with a flux of (372.60 ± 45.12) µg/cm2/h and (474.21 ± 46.64) µg/cm2/h, respectively. Ten percent (w/w) EtOH/IPM binary system was used to investigate the effect of the counter-ions, namely diethylamine (DEA), triethylamine (TEA), ethanolamine (EtA), diethanolamine (DEtA), triethanolamine (TEtA), and N-(2′-hydroxyethanol)-piperdine (HEPP). The cumulative amounts were markedly increased in the presence of the counter-ions, and the highest flux of (1297.53 ± 121.81) µg/cm2/h was obtained by DEA. This was related to the decreased lipophilicity and different physicochemical properties of the ion-pairs. In particular, we proved the formation of an FP/amine ion-pair in solution by 1H-NMR. The results suggest that the counter-ions are more efficient than penetration enhancers. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1826–1837, 2010