ABSTRACT
The purpose of the present work was to study the effect of sodium dodecyl sulfate (SDS), an anionic surfactant, on the iontophoretic transport of a neutral drug hydrocortisone (HC) across hairless mouse skin. The transport studies were conducted using Side-Bi-Side diffusion apparatus and drug concentration in the receptor cell was analyzed using reversed-phase HPLC. A theoretical model was described, tested, and found to agree well with experimental data (R2 = 0.9766). Anodal iontophoresis significantly enhanced the transport of HC compared to cathodal iontophoresis and passive diffusion, suggesting that the transport of the neutral solute occurs via the electro-osmotic flow. The effect of SDS on the transport of HC was highly concentration-dependent and driving mode-dependent. Below the critical micelle concentration (cmc), increasing the concentration of SDS increased both the passive and the iontophoretic fluxes of HC, but the increase was most significant with anodal iontophoresis. Above the cmc, passive transport of HC continued to increase with an increase in the SDS concentration. The transport after anodal iontophoresis, however, reached a plateau and then leveled off. Further increase in SDS concentration decreased flux, suggesting that the transport of micellar-solubilized drug is retarded by anodal iontophoresis, possibly due to electrostatic attraction.
Subject(s)
Hydrocortisone/pharmacokinetics , Skin/metabolism , Sodium Dodecyl Sulfate/pharmacology , Surface-Active Agents/pharmacology , Animals , Biological Transport/drug effects , Female , Iontophoresis , Mice , Mice, Hairless , Sodium Chloride/pharmacology , SolubilityABSTRACT
Benzalkonium chloride (BAK) is a mixture of alkylbenzyldimethylammonium chloride homologs with n-C,2H25, n-C,4H29, and n-C16H33 comprising a major portion of the alkyl groups present. An analytical method for BAK must differentiate and quantitate the homologs in the BAK mixture. Reversed-phase high performance liquid chromatography (HPLC) separates compounds based on their affinity for a nonpolar column, which is a direct correlation to the compounds' polarity. High performance capillary electrophoresis (HPCE), however, separates compounds in an electric field according to their charge and size. The BAK homologs are suitable for separation by either of these methods because their polarity and sizes differ significantly. The HPLC method employed a mobile phase of 60% acetonitrile and 40% 0.1 M sodium acetate buffer pH 5 pumped at 1.0 ml min(-1), a 4.6 x 250 mm cyano column with 5 microm packing, and UV detection at 254 nm. The HPCE method utilized a run buffer of 30% acetonitrile and 70% 0.05 M sodium phosphate pH 3.06, a 50 microm x 20 cm open silica capillary, 7.5 kV electric field and UV detection at 214 nm. Both HPLC and HPCE demonstrated good linearity in the range of 0.025 to 0.8 mg ml(-1) with r2 values of approximately 0.99. The HPLC method produced good separation of the homolog peaks with a total analysis time of 25 min. HPCE run time was less than 5 min and demonstrated good separation of the three homologs. The HPLC method, however, was superior to HPCE in the areas of sensitivity and precision. The HPLC has been extensively used in the routine quantitation and qualitation of benzalkonium chloride concentrations in various products; however, long analysis times make this method inefficient. The HPCE method produced comparable results to the HPLC method but with much shorter analysis times. An HPCE analysis method, as presented here, may prove to be a much more useful and efficient method for the analysis of benzalkonium chloride and its homologs.
