Correlation of water and lidocaine flux enhancement by cationic surfactants in vitro.
The penetration of radiolabeled water and lidocaine through human epidermis was studied simultaneously using a flow-through apparatus under infinite-dose conditions. The donors were suspensions of lidocaine in propylene glycol:water mixtures containing cationic surfactants of varying alkyl chain length from three classes: alkyl dimethylbenzyl ammonium halides, alkyl trimethyl ammonium halides, and alkyl pyridinium halides. Each skin sample served as its own control; each was subjected to sequential treatments of control formulation with no surfactant, test formulation, and then a repeat control. Higher surfactant concentration resulted in greater enhancement ratios for both permeants. Peak surfactant enhancement effects were seen at alkyl chain lengths of 12 or 14 carbons. Strong correlation was noted between the enhancement ratios of water and lidocaine. Water permeation can serve as a predictor of the effects of surface-active compounds on the permeation of drugs. The data suggest that water and lidocaine utilize the same pathway through the horny layer.
Kushla
G P
GP
Department of Pharmaceutics, Rutgers College of Pharmacy, Piscataway, NJ 08855-0789.
Zatz
J L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000473:Alkanes / Q000737:chemistry; D001692:Biological Transport / Q000502:physiology; D002412:Cations / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008012:Lidocaine / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D014677:Pharmaceutical Vehicles; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology*; D014867:Water / Q000378:metabolism*
D000473:Alkanes; D002412:Cations; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; D014867:Water; D008012:Lidocaine