DIFFERENCE IN THE ENHANCING EFFECTS OF ULTRASOUND ON THE SKIN PERMEATION OF POLAR AND NONPOLAR DRUGS

The effect of ultrasound (150 kHz, 111 mW/cm(2)) on the permeability o f isosorbide dinitrate (ISDN) and antipyrine (ANP) through excised hai rless rat skin was evaluated using an Arrhenius plot, The permeability coefficients of ISDN across skin (at various temperatures) in the pre sence and absence of ultrasound were virtually isolinear on the Arrhen ius plot, It has been suggested that the temporal increase in the ISDN flux, which was observed when ultrasound was applied in our previous study, was only a result of the thermal effect of ultrasound, i.e. an increase in the temperature of the donor solution, On the other hand, ultrasound influenced the Arrhenius plot of ANP, suggesting that the e nhancement effect for ANP permeation could be not explained only by th e thermal effect of ultrasound, In addition, the effective diffusion ( D) and partition coefficients (K) of ISDN and ANP mere estimated using their skin permeation profiles across the ultrasonic pretreated skin, The coefficients of ISDN with ultrasonic pretreatment were comparable to those without pretreatment, On the other hand, the D value of ANP with ultrasonic pretreatment was increased about 4 times by ultrasonic pretreatment, in spite of an insignificant change in the K value, The se results suggest that the ultrasound used in the present study incre ased the effective diffusivity across the aqueous region in the stratu m corneum to enhance the skin permeation of the polar compound, ANP.