利用物化性質影響 sildenafil 的穿皮效果
目的 : Sildenafil 是藉由口服抑制 cGMP-phosphordiesterase ，減少 cGMP 代謝以擴張血 管達到治療陰莖勃起功能障礙的疾病，雖然此藥物的專一性極高，但仍有低血壓的負作 用，故考慮局部投與 sildenafil 取代口服使用，以減少全身系統血中濃度避免不必要的 副作用。
方法 : 利用裸鼠 (BALA/c-nu) 的新鮮皮膚放在 Franzcell 上進行 sildenafil 的穿透實驗。在定量上則實用 UV224nm 波長與內部標準品 ethylparaben 的 HPLC 條件來作為 sildenaf il 穿透定量，其最低偵測濃度為 5ng/ml ，檢量線範圍從 5-500ng/ml ，而 sildenafil 和 eth ylparaben 的留滯時間分別為 8.1 與 10.2 分鐘。
利用 sildenafil 隨 pH(4.0-12.0) 改變其溶解度與擬似分配係數，並利用 5 種助溶劑 solu1， solu2 ， soul3 ， soul4 和 soul5 與 3 種促進劑 en1 ， en2 ， and en3 兩種方法，相互 搭配促使穿透流量的上升。
結果 : Sildenafil 的穿透係數會隨 pH 從 4.0 到 12.0 而變化，其變化主要隨著擬似油水分 配係數在中性 91.25*4.44> 酸性 0.644*1.08* 鹼性 0.68* 1.23 。其次本實驗使用的 3 種促 進劑中以 en1 能明顯的將擬似穿透係數從 1.26*0.24*10-6 cm/sec 增加為 4.30*0.79*10-6 cm/sec ，助溶劑雖然使 sildenafil 的溶解度增加，其穿透流通量仍介於 0.03~0.063 ng/c m2/sec 之間。然而利用促進劑與助溶劑搭配下能使穿透流量增加，其中最高穿透流量 0 .31 ng/cm2/sec 是利用 en1 與 solu4 或 solu5 搭配下所促成的穿透流量。
結論 : Sildenafil 的物化性質如溶解度、擬似油水分配係數、和擬似穿透係數會隨 pH 3.0 到 12.0 的變化而改變。實驗上助溶劑可增加 sildenafil 的溶解度，促進劑 en1 可增加 s ildenafil 的擬似穿透係數；然而在適當的助溶劑中如 solu4 或 solu5 與 en1 並用下， silde nafil 的穿透流量可從 0.05 ng/cm2/sec 增加為 0.31 ng/cm2/sec 。
Effect of Physico-Chemical Property on Sildenafil Transdermal Permeation
Purpose: In order to decrease the side effect of Sildenafil (Viagra*), which dilated vessel by inhebiting cG MP-phosphodiesterase and treated penis erectile dysfunction, sildenafil for topical administration was alter native delivery instead of oral route.
Method: Fresh skin of nude mouse (BALA/c-nu, 8weeks) was used in the penetration experiment of Franz cell for sildenafil. The apparent permeability coefficient of sildenafil was estimated in different pH 4.0~12.
0 range by HPLC method that UV set on 224nm and 5-500 ng/ml calibration curve. It was found 5ng/ml of the limited of quantation for sildenafil with ethylparaben as internal standard, and the retention time of sild enafil and ethylparaben were 8.1and 10.2 min, respectively.
In order to improve the flux of sildenafil, modification of pH environment and addition of 5 solubilizers, so lu1, solu2 solu3, solu4, and solu5 cooperated with 3 enhancers, en1, en2, and en3 were used to examine the solubility, apparent partition coefficient, and apparent permeability coefficient.
Result: The apparent permeability coefficients of sildenafil were changed within pHs. It was found that the apparent permeability of sildenafil was followed the apparent partition coefficient changed as neutral, 91.2 5*4.44>acid, 0.644*1.08*basic, 0.68*1.23 pH range. And only en1 enhancer could increase the apparent th e apparent permeability coefficient from 1.26*0.24* 10-6cm/sec to 4.30*0.79*10-6cm/sec. Following 5 sol ubilizers addition, the solubility of sildenafil could all increase, though the flux was still in the same range, 0.03~0.063 ng/cm2/sec. In addition, the enhancers cooperate with solubilizers to increase the flux up to 0.3 1ng/cm2/sec by en1 with solu3 or solu4.
