In Vitro Investigation On The Ferulic Acid Transdermal Delivery Behavior: Effect Of Enhancers And Chitosan-based Membranes

Transdermal drug delivery system(TDDS) is a promising topic in the pharmacetic industry. To shorten the developing time, authorized drugs were often chosen as model medicine when developing a new TDDS. Therefore, the key problems in the TDDS are the development of proper auxiliary materials such as carriers, enhancers and bone materials. In this thesis ferulic acid(FA) was selected as the model medicine for the wide therapy application in chronic nephritis et al. Therefore this thesis was focused on auxiliary materials for FA TDDS.In order to improve the skin penetration amount of FA, transdermal enhancers were employed. The results showed that the skin penetration amount of FA was raised with the present of aznoe, thiozone, and propanediol. Among them, azone was the best one and the skin penetration amount of FA was increased by 10 times. But the retardation time of azone was the longest, about 9 hours. The retardation time was cut down by using the mixture of azone and propanediol with the ratio of 1:1. The improved penetrated amount of FA was obtained at the same time. Fluorescence microscopy was applied to observe the transdermal route of FA. The result showed that when resolved in water and alcohol FA penetrated through intercellular lipid and hair follicles; with the present of azone, thiozone, and propanediol, FA penetrated through not only intercellular lipid and hair follicles, but also keratin.Optical microscopy, 13C NMR and ATR-FTIR were used to study the mechanism of transdermal enhancers. The results showed that methanol and chloroform could extrude out the lipid in the stratum corneum(SC), so the SC barrier was reduced; azone, thiozone, methanol and chloroform could interact with lipid and increase the mobility of lipid, therefore reduce the obstacle of penetration.Another focus of this thesis was on the property study of chitosan membrane carrier. Chitosan was easy to film, has good penetrating properties and was the absorption enhancer of some drug. The FA release the properties of chitosan membrane were carried out. On the modified Franz cells. The results showed both molecular weight and crosslinking reagent effected the FA release property. For non-crosslinking chitosan membranes, the higher the molecular weight(M), the more the release amount of FA. For crosslinking chitosan membranes, there may have a critical molecular weight MC. When M＜MC, the FA release velocity increased with the increase of molecular weight; When M＞MC, the FA release velocity decreased with the increase of molecular weight. A higher penetrated amount and a larger FA release velocity were obtained in the hydrophilic glycolchitosan membrane...