5-fluorouracil微乳劑局部與經皮穿透性之研究

Study of 5-fluorouracil-loaded microemulsion in dermal and transderml drug delivery

鄒欣燁(Hsin-Yeh Tsou)

指導教授 ： 吳寶珠

高雄醫學大學/藥學院/藥學研究所/碩士(2011年)

摘要

5-fluorouracil為一種抗代謝(antimetabolite)藥物，口服給予吸收不穩定，因此多以注射給藥，然而，藥物會快速地分佈到身體的循環系統而造成全身性毒性，所以擬藉由經皮輸送系統局部給予藥物來治療淺層性的皮膚癌，並降低全身性的副作用。將5-fluorouracil製成微乳劑型，利用體外穿透實驗來評估藥物的累積穿透量以及在皮內各層的含量，在處方的評估中，利用ethyl oleate 來作為處方的油相，可以使處方成形的機會較大，且設定的HLB值較為廣泛。其中處方34 ( 30%界面活性劑、30%輔助界面活性劑、30%油相及10%水相)的組成具最多的皮內藥物含量，顆粒大小僅10.9?b1.6 nm，且黏度小，藥物濃度(0.2%)雖只有市售品(5%)的二十五分之一，但於表皮層的藥物含量與市售品含量相近，分別為16.69?b6.28及11.51?b2.79 μg/mL。接著探討此處方於不同時間的穿透累積量與皮內含量來做比較，並利用不同的動物腹部皮膚進行比較，由結果得知，可以利用微乳劑的劑型，成功包覆模式藥物，可降低藥物的使用量卻也能達到理想的局部效果。

關鍵字

微乳劑 ； 經皮吸收 ； 皮膚癌

並列摘要

Fluorouracil (5-FU) is a drug that is a pyrimidine analog and also an antimetabolite drug which is used for topical treatment of skin cancer. However, 5-FU can cause systemic toxicity by intravenously, because it quickly spread to the circulatory system of the body, treat superficial layer of skin cancer by topical percutaneous delivery system is necessary, and also reducing the possibility of systemic toxicity.
EfudexR is the commercial product of 5-FU cream, it can be used topically for treating actinic keratoses, Bowen's disease, superficial basal cell carcinomas and some type of the underlying skin disease. Present commercial formulations of 5-FU is an O/W cream that coating on the hands and arms where the skin is less permeable but large amount at dermal layer.
In this study, the microemulsion was used as transdermal vehicle. The influence of components such as level and HLB value of surfactant, type and level of cosurfactant, the ratios between the components and the drug concentration on the physical characterization (droplet size and viscosity) and permeation capacity of drug were evaluated for searching an optimum formulation for 5FU. The acumulative amount of epidermis layer ranged from 80.55±7.17 to 0.87±1.35 μg/cm2 indicating that the permeation parameters of 5-FU from microemulsions were significantly influenced by the composition of microemulsion. It was found that microemulsions containing surfactant with hydrophilic-lipophilic balance (HLB) value of 6.0 had higher amount of drug at skin layer. The amount of surfactant in microemulsions increased, viscosity of microemulsions increased. However, the microemulsion with ratio of S/Co/O at 1:1:1 showed highest amount at skin layer and the smaller size and viscosity. The acumulatve amount at skin of microemulsion was comparable to the commercial cream, although the drug concentration of microemulsion was 1/25 of commercial cream, it had promote acumulatve amount at skin layer. The potential of microemulsion compared to an ointment as a suitable carrier for dermal delivery of 5-FU was determined.

並列關鍵字

5-fluorouracil ； microemulsion ； ethyl oleate

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