Fluvastatin is the first synthetic HMG-Co A reductase inhibitor to be approved for clinical lipid-modifying therapy. In order to achieve and maintain an adequate concentration of drug at the side of action for a prolonged period of time so as to improve the therapeutic efficiacy, in this work, we attempt to develop a transdermal delivery system by the use of FAPG ointment dosage forms. We investigated the effect of variation in the composition of ointments on the viscosity of ointments and drug release. The physicochemical properties of ointments were determined by Cone and Plate viscometer.
The effect of ointment physicochemical properties on the release of fluvastatin from ointment bases and the percutaneous penetration through rat skin were discussed by in vitro studies. The results indicated that ointments are referred to as pseudoplastic flow and the increase in the drug release rate was inversely proportional to ointment viscosity. In in
vitro permeation studies, the transdermal penetration rate of fluvastatin is much lower than the release rate of the drug from FAPG bases. It can be seen that fluvastatin cannot permeate through the rat skin in significant amount after application. The absorption enhancers were applied to increase the skin penetration of fluvastatin. Among the surfactants, the penetration efficiency of benzalkonium chloride and sodium lauryl sulfate were better than Tween 80 and Span 40. The concentration 1 % of enhancers was found to be the most efficient in all case. Moreover, it did not show any significant difference in the penetration efficiency between to use the absorption enhancers to pretreat the skin before the application of ointment and to take absorption enhancers as additives to incorporate into FAPG ointments.The above results will be helpful to possible development of the other lipid-regulating drug transdermal delivery systems. Fluvastatin是用於臨床上脂質調節治療之第一個全合成HMG-Co A還原抑制劑，為了要達到並維持長時間在作用部位的適當治療濃度以增進治療效果，本研究嘗試使用脂肪醇與丙二醇混合基劑軟膏來發展經皮輸移系統，探討不同軟膏配方對軟膏黏稠度與所含藥物釋離的影響；其中軟膏的理化性質是以Cone and Plate黏度計來檢測，軟膏的理化性質對其所含藥物的釋離與經皮吸收的影響則以大白鼠皮的體外實驗來評估。結果指出，本軟膏是屬於假塑性流體且其藥物之釋離與軟膏之黏稠度呈反比的關係。在體外的藥物經皮穿透實驗中發現，fluvastatin的經皮輸移速率遠低於藥物自脂肪醇與丙二醇混合基劑軟膏的釋出速率。