The effect ofphonophoresis on transdermal delivery of sinomenine hydrochloride gel in vitro

Abstract

：Objective To study theeffect of phonophoresis on transdermal delivery of sinomenine hydrochloride ( SH ) gel invitro. Methods Ultrasound at one of two frequencies ( 800 kHz or 1 MHz) was applied with asonicator with a transducer in this study. The skin of male Sprague-Dawley rats was usedas the model and SH gel was used as the ultrasound couplant. The permeation rate of SH wasdetected using a modified Franz diffusion cell maintained at 32±0.5℃ and filled with 20% polyethylene glycol 400 physiological salinesolution. The transdermal phonophoresis experiments were carried out in five groups: GroupTa, f=800 kHz, / = 0.75 W/cm2, t = 10 min:Group Tb,f=1 MHz,I=0.7 W/cm2, t=10 min; GroupTc,f=1 MHz,I=0.35 W/cm2, t=10 min; Group Td,f=800 kHz, I = 1.5 W/cm2, t = 10 min and GroupTc,f=800 kHz, I=1.5 W/cm2,t=5 min. There was also a control group (C) in which the SH wasallowed to diffused passively. Samples were withdrawn at the indicated intervals and theconcentration of SH was determined by high-performance liquid chromatography. Thetransdermal parameters such as average accumulated delivery quantity per unit area Q8h,average transdermal steady delivery rate J, and Tlag were calculated. Results The Q8h andJs of the control group were 20.65±10.23 μ/cm2 and 3.02±0.11μ/cm2/h respectively. Thephonophoresis parameters in groups Ta and Tb were, on average, significantly higher thanin the control group. The parameters in group Tb were significantly larger, on average,than in Te. In group Td the parameters were significantly larger than in groups Ta and Te.Conclusions The results show that phonophoresis can enhance the transdermal delivery ofSH. Phonophoresis variables such as frequency and time influence its effects on drugpermeation. Almost no change was observed in the structure of the skin afterphonophoresis, though under a scanning electron microscope the surface of the corneumappeared rough and porous. Phonophoresis is there-fore an effective and safe method for SHtransdermal delivery, and the effect is positively relation with the applied intensity andexposure time. Key words: Sinomenine hydrochloride; Percutaneous penetration; Phonophoresis