Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B  

作　　者：TIAN Qing-ping LI Peng XIE Ke-chang 

机构地区：[1]Key Laboratory of Coal Science and Technology, Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, P. R. China [2]Department of Pharmacy, Shanxi Medicial University, Taiyuan 030001, P. R. China

出　　处：《Chemical Research in Chinese Universities》2009年第1期86-94,共9页高等学校化学研究（英文版）

基　　金：Supported by the Grant from the Agriculture Technologies R & D Program of Shanxi Province, China(No. 2007032013).

摘　　要：In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.

关 键 词：MICROEMULSION Transdermal drug delivery Amphotericin B PH 

分 类 号：R962[医药卫生—药理学]