| Popis: |
In vitro iontophoretic transdermal delivery (ITD) of a tripeptide, enalaprilat (EP) and a non-peptide, cromolyn sodium (CS), across frozen hairless guinea pig (HGP) skin were investigated. Parameters for optimization of ITD included the influence of ionic strength (μ), buffer type and size, drug loading in the donor and the effect of pH. Drug permeation into the receptor compartment was monitored using HPLC assay methods developed for the study. An optimum μ of 6.66 mM in acetate buffer was found necessary for efficient ITD of CS. An exponential decrease in the flux of CS was observed with an increasing μ. Buffer ions larger than acetate ions inhibited the transport of CS ions. With an increase in the donor concentration of CS, a hyperbolic relationship for the increase in flux was observed. For EP, permeation was not detectable when μ was increased to greater than 31 mM in phosphate-buffered solution. With an increase in pH above the p K a 1 (3.55) for EP, a linear decrease in flux was observed. Higher drug loading of EP in the donor compartment provided better permeation. Effect of freezing of HGP skin on the iontophoretic delivery of EP and CS was also evaluated. Flux values for either of the drugs studied were similar when frozen or fresh skins were used. Reversibility studies indicated that no gross current induced permeation changes occurred with the HGP skin. Passive permeation of either of the drugs investigated was negligible. |
