探討以乳膏劑型乘載薑黃素衍生物的穩定性以及穿透效率

Abstract

皮膚結構可分為三層：表皮層、真皮層、皮下組織，其中最外層為沒有血管分佈的表皮層，而真皮層及皮下組織才有血管分佈。當以皮膚局部給藥時，藥物需先通過表皮層再到達真皮層才能進到循環系統中。此給藥途徑的穿透距離短、運用方便。然而表皮層中的角質層不只阻隔外界干擾也阻擋藥物穿透，導致此給藥途徑的療效有限。為了解決此問題，可以依Fick’s law延伸以下策略：（1）物理性破壞角質層進而減短藥物穿透所需距離、（2）被動性，其中分為提高給藥量或是添加滲透促進劑以幫助藥物分佈、擴散、（3）其它方式，例如：改變藥物結構、以疏水性物質包覆藥物等等，來提升藥物穿透效率。 本研究為了提高一種化合物主成分所製成局部塗抹劑型之穿透效率，分別或同時藉由「提高劑型的乘載藥量」和「添加滲透促進劑」這兩種被動性策略來進行此一劑型的改良，以提高穿透效率。在滲透促進劑的選擇上，根據藥物性質及劑型所需，我們選擇DMSO、Tween 80、Urea、Isopropyl myristate（IPM）這幾種並於一個月穩定性的離心試驗比較中篩選出IPM、DMSO組別，以進行穿透試驗。其中於0.1%藥物下，滲透促進劑無法提升穿透效率，不過在0.4%藥物下，兩組的穿透效率提升約20%，因此進一步提高IPM、DMSO濃度，以測試穿透效率能否再提升。不過IPM組效果並不明顯，而提高DMSO的量能提升一倍的穿透效率。我們發現單純提高承載藥量本身在in vitro穿透實驗中並無法提升穿透效率，必須配合滲透促進劑的添加，方能有效地增加藥物的穿透率。綜合以上，於此劑型中， IPM和DMSO的組合運用應為最適合濃度以幫助藥物達最佳分散效果，不過搭配兩者時，in vitro穿透效率沒有再提升。

The structure of skin is classified to three layers: epidermis, dermis, subcutaneous tissue. Epidermis is the outermost, and there isn’t any blood vessel in epidermis as found in dermis and subcutaneous tissue. Therefore, drug in topical formulation should pass epidermis first, then reach dermis, and enter to circulation system finally. The stratum corneum of epidermis comprised of the dyed cells in the outmost layer protects the body from environment that also blocks the penetration of drugs in topical formulation. Therefore, the efficiency of topical formulation for skin disease is limited. To resolve the problems, several strategies have been developed according to Fick’s law. These strategies are divided into three parts: first, using physical force to damage the stratum corneum; second, increasing the drug amount or adding penetration enhancers to enhance the distribution and diffusion of drug; third, developing nanocarrier to encapsulate the drug, etc. In this study, two passive strategies were adopted to enhance the penetration efficiency of one compound (named as CL) in topical formulation. One is to increase the amount of drug in formulation and the other is to add penetration enhancers. We found that simply increasing the concentration of CL didn’t increase the penetration efficiency. For the penetration enhancers, we examined the efficacy of DMSO, Tween 80, urea, and Isopropyl myristate (IPM). According to the results of centrifugation test, we further chose the group of IPM and DMSO for penetration test. The results of Franz cell study showed that the increase in the combination of IPM and DMSO in the formulation not only could help CL dispersing but also improve the penetration efficiency.