A Research of Drug Delivery System by Time-Varying Electric Field - Development of high performance electric infiltration anesthesia -

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A Study for the basic mechanism of the high frequency AC iontophoresis (HFIP) has been pursued. First, we examined the efficiency of the by measuring the impedance of the solution in the receptor side of the diffusion cell. Several frequencies and a few voltages of external sinusoidal electric fields were used to evaluate the frequency dependency and the voltage dependency of the HFIP.The permeable efficiency of the saline by HFIP increased with the increase of the external electric voltage up to 〜15 V and leveled off at the voltages larger than 15 V. A physical model was proposed to explain the mechanism of HFIP. The theory of physical model is as follows ; the ion-dipole interactions are broken by the vibrational energy of the ion supplied by the external electric field. The decrease of the effective Stokes radius causes the increase of the diffusion coefficient of the ion.The permeable efficiency of the lidocaine by HFIP showed the maximum value at the frequency 〜300 Hz when the voltage was 30 V. A theoretical model that the rotational energy of the ion supplied by the external electric field break the 'ice burg' of the surrounding water molecules and that the decrease of the effective Stokes radius follows it.It has been cleared that the shape of the external electric field affects the efficiency of the HFIP. A convergent shape electric field transport ions more effectively than the divergent or the parallel electric field.We have developed a method of measuring the concentration of the lidocaine under the rat's skin with the microdialysis probe. This method will give us data of the drug distribution under the skin.The HEIP of the 20 % lidocaine effectively anesthetized the forearm nerve without adverse events. It can be concluded that the HFIP is a new and safe technique for the transdermal drug delivery.