- 學位論文
共溶媒凝膠系統對要物穿皮滲透之影響解析
The evaluation of affection of the drug in cosolvent gel system penetrate through epidermis
摘要
本研究的目的是針對臨床上以注射方式給藥治療陽痿的藥物 papaverine﹐探討其發展成局部穿皮吸收的可能性。我們利用Simplex lattice 實驗設計法設計出兩個共溶媒系統（water-ethanol-PG﹐water-ethanol-PEG 400）﹐配合鹽態及原形藥物觀察其對體外穿皮滲透的影響性。並計算其溶 解度?穿透率?穿透係數且利用DESIGN-EXPERT以統計數據分析其共溶 媒之間的相互作用。 結果顯示對於兩種形態的藥物酒精是最有效益的穿透促進劑﹐在兩種 形態的藥物中﹐PG在共溶媒佔10至20%時有協同效益﹐但超過30%以上 則無促進的效果。另外在PEG 400系列﹐雖然酒精仍有改善的效果﹐但在 整個系列中看不到促進的能力﹐這個結果證明PEG 400會降低滲透係數﹐ 由於增加藥物在共溶媒water-ethanol-PEG 400的分配係數﹐因此反而降低 藥物擴散進入皮膚。本研究更進一步利用regular溶液理論以及內聚參數概 念﹐解釋分配係數與滲透係數有直接的相關。 為了增加溶解度﹐我們分別在鹽態與原形藥物中加入非離子性界面活 性劑（Pluronic F127）及離子性界面活性劑（Carbopol 934）﹐結果發現只 有原形藥物在離子性界面活性劑存在下﹐可增加1至3倍的穿透﹐因此認 為water-ethanol-PG在40/30/30比例時﹐可以作為治療陽痿穿皮吸收劑型 的促進劑。
並列摘要
The purpose of this study was focused on the model drug papaverine HCl for erectical dysfuction by intracavernous injection on clinical , to explore that possibility of topical transdermal administration. The influence of the in vitro percutaneous penetration of the salt and free forms of model drug were examined on two cosolvent series systems, consist of (water, ethanol and propylene glycol (PG)), and (water, ethanol and PEG 400) by simplex lattice experimental design. In addition, the solubility, flux and permeation coefficient through nude mice skin of the drug were caculated and was quantitatively analysized interaction among water, ethanol, PG, PEG 400, cosolvently, by statistical parameters by DESIGN-EXPERT. The results have shown that ethanol effective enhance on series dosage forms of both salt and free types . Among series dosage forms, 10%-20% of propylene glycol had synerigic effect with ethanol up to 30%. On the other hand, in PEG 400 series, although had increment ability by ethanol, the total enhance ability did observe. This was indicate that the addition of PEG decreased the permeability coefficient and increase the partition coefficient of drug in vehicle of water-ethanol-PEG 400 system, to slow the diffusion of the drug into skin. Furthermore using regular solution theory and the cohesion parameter concept, it could explain that partition (Km) and the permeability coefficients (Kp) have directly relation. In order to increase solubility of drug in dosage form, different prescription of salt and free forms of drug were adding by non-ionic Pluronic F127 surfactant and ionic Carbopol 934. The results appeared that only free form of drug in ionic Carbopol gel have enhancement around 1-3 times. The composition of water-ethanol-PG (40/30/30) have most potential enhancement for impotence treatment by tansdermal delivery.