- 學位論文
Captopril微乳劑型之經皮輸藥系統
In vitro penetration study of topical captopril microemulsion delivery system
摘要
Captopril為一種抗高血壓藥物，屬於升壓素轉化酵素抑制劑 (Inhibitor of angiotesin converting enzyme, ACE inhibitor ) 是一具獨特作用機轉之抗高血壓治療劑，其機轉主要是抑制angiotensin I 轉變成 angiotensin II，除此之外，這一類的藥物會抑制aldosterone的分泌、鈉滯留以及水滯留 (Akhras and Jackson, 1991)。Captopril是糖尿病患的第一線抗高血壓用藥，因為它會增加細胞對於beta-insulin的敏感性並具有保護腎臟的能力。而且此類藥物較不會有一般降壓劑經常產生之副作用如姿態性低血壓、眩暈、頭痛、心悸及便秘等症狀；故本研究以Captopril為模式藥來研製其經皮輸藥製劑。 本文主要是探討使用microemulsion來包覆作為transdermal vehicle，藉由評估不同HLB值、不同油類、不同surfactant、不同co-surfactant、不同藥物濃度對於處方的影響，初步篩選出累積穿透量較佳的處方比例。接著再評估數種enhancer對於累積穿透量是否有實質上面的幫助，再藉由適當的體外穿透實驗來評估處方對於累積穿透量的影響，發現通透率會隨著藥品濃度的增加而增加。 在體外經皮穿透方面，根據不同組成成分和比例的實驗結果，篩選適當的處方，進一步探討其經皮穿透量。其結果顯示Captopril在HLB值為11.0時且含有isopropyl myristate, isopropyl alcohol, 0.5% EDTA disodium, 1% acetic acid處方中穿透效果最好，藥物的包覆濃度約為3.5% (350 mg溶於 10 ml microemulsion中) 在刺激性研究方面，主要是藉由病理切片和色差儀來評估製劑對於皮膚刺激性的影響，結果顯示，以微乳劑型來當作captopril的carrier能夠降低captopril的刺激性。色差儀評估的發紅參數的確有降低的趨勢，以病理切片來觀察的話，使用solution和microemulsion兩者於顯微鏡的觀察下有些許的不一樣。
並列摘要
Captopril is an anithypertension agent belonging to the angiotensin converting enzyme inhibitor (ACEi). The mechanism of captopril is to avoid angiotensin I transform to angiotensin II and reduce vasopressin level of blood. Besides, ACEi can also decrease aldosterone secretion, salt retention and water retention. Furthermore, captopril is the first-line therapy regimen for DM patients because of the increasing sensitivity for cell to beta-insulin and the protection ability of kidney. The side effect of this kind of antihypersion agent is less such as, headache, constipation and so on. Therefore captopril was selected as model drug in this study. This study is to investigate to encapsulate Captopril with microemulsion, with different HLB value, different oil, different surfactants, different co-surfactants, and different drug concentration and figure out whether these factors affect the total permeation amount or not. After that, we evaluate some kinf of enhancers to find out if those can improve the total permeation amount. Lastly, we use appropriate method to evaluate in vitro total permeation amount. In the in vitro study, according to the 24h accumulative permeation amount. We select isopropyl myristate as the oil phase, isopropyl alcohol as the co-surfactant, D2W with 0.5% EDTA disodium and 1% acetic acid. The materials above mentioned are the optimal compositions and the drug concentration is around 3.5%. In the irritation study, according to the result of colorimeter and pathological section. We found out that while microemulsion used as carrier of captopril could reduce the irritation to skin. The parameter of colorimeter showed that the flush phenomenon of microemulsion with captopril was quite lower than this of solution with captoril.