Enhanced transdermal delivery of dihydrotestosterone using the combination strategy of iontophoresis and prodrug / 国际药学研究杂志

ABSTRACT

Objective To enhance the transdermal delivery of dihydrotestosterone(DHT)and to make the delivery controlla?ble,which would enable personalized administration of DHT to pediatric patients. Methods A hydrosoluble,ionizable prodrug of DHT,dihydrotestosterone dimethylglycine ester hydrochloride(DHT-DG),was synthesized,characterized and its physicochemical properties were determined. DHT And DHT-DG were formulated into hydrogel,respectively,and the transdermal delivery of each compound across fresh porcine ear skin with or without iontophoresis was evaluated. Results Application of current(0.5 mA/cm2)to 2.5%DHT-DG hydrogel for 8 h enabled(226.91±45.62)nmol/cm2 accumulative amounts of DHT-DG across fresh porcine ear skin, which was much higher than the amount of DHT delivered from 2.5%DHT hydrogel without iontophoresis,(10.45±3.63)nmol/cm2. More than 80%delivered amount of DHT-DG was hydrolyzed into its parent drug DHT. The steady state flux of DHT-DG was found af?ter the application of iontophoresis for 2 h,and the accumulative amounts of DHT-DG could be modulated by drug concentration and current intensity. Conclusion Combination strategy of iontophoresis and prodrug can enable fast controllable transdermal delivery of DHT.