Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of celecoxib through human skin.
The aim of this study was the comparison of three different formulations (gel, o/w emulsion, oleagenous cream) and two penetration enhancers (oleic acid and menthol) as vehicle systems for celecoxib in respect of release and penetration through excised human skin in vitro. The influence of the vehicle on the release rate was studied in vitro using a cellulose acetate membrane. The release rate could be increased by up to 6.5 and 2.5 times with gel and o/w emulsion compared to oleagenous cream respectively. Further in vitro penetration measurements using human skin on Franz diffusion cells were performed with and without oleic acid and menthol as enhancers. It was shown that the penetration rate is strongly dependent upon the enhancer type and concentration but not on the vehicle itself and could be increased by 48% when 5% oleic acid was used in oleagenous cream. In all formulations tested, celecoxib was released and penetrated into human skin more quickly and to a greater extent from the gel formulations. There is no topical formulation available of celecoxib and its penetration properties through human skin have not been investigated. Since celecoxib creates some gastrointestinal disturbances, topical formulations of celecoxib preferably in gel form including 5% oleic acid could be suggested as an alternative.
Yener
G
G
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey. gulyen@superonline.com
Gönüllü
U
U
Uner
M
M
Değim
T
T
Araman
A
A
D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004655:Emulsions; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007785:Lactose / Q000031:analogs & derivatives*; D008565:Membrane Proteins; D008747:Methylcellulose / Q000031:analogs & derivatives*; D009824:Ointments; D010078:Oxazines; D014677:Pharmaceutical Vehicles; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004655:Emulsions; D005782:Gels; D007527:Isoenzymes; D008565:Membrane Proteins; D009824:Ointments; D010078:Oxazines; D014677:Pharmaceutical Vehicles; D011720:Pyrazoles; D013449:Sulfonamides; D008747:Methylcellulose; C071191:MK 458; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007785:Lactose; D000068579:Celecoxib