利用Response Surface Methodology方法來評估美洛西卡在體外穿透之研究   全文下載

In-Vitro Evaluation of Meloxicam Permeation Using Response Surface Methodology

不同機轉的經皮穿透促進劑（如azone、sodium lauryl sulfate和menthol）以uniform deign和response surface methodology來評估美洛西卡經皮吸收處方穿透鼠皮的影響，Uniform design應用在系統性模式的處方有三個影響因子：azone （X1）、sodium lauryl sulfate （X2）和menthol （X3），美洛西卡經皮吸收結果顯示azone有最大的影響性，其次為sodium lauryl sulfate和menthol，若以零階次速率輸送藥物，為維持治療效果美洛西卡經皮凝膠穿透速率約為400毫克/小時/平方公分。實驗結果顯示在美洛西卡凝膠中含azone 4-6%有較高的穿透速率和較短的延遲時間；含sodium lauryl sulfate0%到12%則穿透速率和48小時累積穿透量隨之增加，而延遲時間隨之減少；menthol則為處方提供較短的延遲時間。為了確認假設模式的預測能力，利用預測處方並執行實驗來檢測，結果顯示預測處方能應用於經皮穿透系統。

The influences of combination of different mechanisms of penetration enhancers (such as azone, sodium lauryl sulfate and menthol) on the percutaneous absorption of meloxicam formulations through rat skin were investigated using uniform deign and response surface methodology. The uniform design was applied to prepare systematic model formulations which were composed of three formulation factors: azone (x1), sodium lauryl sulfate (x2), and menthol (x3). The result showed that azone had the highest potential influence on the penetration absorption of meloxicam, followed by sodium lauryl sulfate and menthol. With zero-order delivery, the required flux of meloxicam gel to maintain a therapeutic concentration was about 400 μg/hr/cm2. The result showed that the optimal addition concentration of azone at 4% to 6% could be obtained at high penetration rate and short lag time of meloxicam gel. It was shown that as the concentration of sodium lauryl sulfate increased from 0% to 12% the flux and cumulative amount at 48 hr increased and lag time decreased. On the other hand, menthol had the effect of a shorter lag time. To validate the predictive ability of the hypothesized model, the predicted formulations were prepared and penetration experiments were performed. The predicted formulations were developed for the transdermal drug delivery system.