Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Pharm Res. 2022 Oct;39(10):2421-2430. doi: 10.1007/s11095-022-03238-6. Epub 2022 Mar 29.
The aim of this study is to convert tretinoin (Tr), an active pharmaceutical ingredient (API), into ionic liquid for improving aqueous solubility and permeability of Tr in transdermal drug delivery applications.
Three ionic liquids of Tr (TrILs) were synthesized through neutralization reactions, which were characterized to confirm the compositions and ionic interactions. The in vitro drug release studies and skin penetration tests were carried out to assess the performance of formulations containing TrILs.
The TrIL formed by choline and Tr at the molar ratio of 2:1 (2[Ch][Tr]), was found to have prominent solubility, stability as well as permeability. In contrast with the insoluble Tr, 2[Ch][Tr] presented as clear and transparent aqueous solution even after diluted to 14%. The aqueous solution of 2[Ch][Tr] demonstrated better permeation effect, of which the solution with 20% of 2[Ch][Tr] showed the optimal delivery efficiency in both epidermis (2.09 ± 0.18‰) and dermis (3.31 ± 0.48‰), realizing the improvement on the permeability of API. Meanwhile, TrILs can be easily fabricated as o/w emulsions as transdermal formulation. The emulsions are also able to improve the skin permeability of Tr, though the enhanced effect is inferior to TrILs solutions.
Ionic liquid technology can be used to improve solubility and permeability of Tr, providing a high potential strategy for the development of topical formulations and the desired transdermal application of drugs.
本研究旨在将维 A 酸（Tr）转化为离子液体，以提高其在经皮给药应用中的水溶解度和渗透性。
通过中和反应合成了三种维 A 酸离子液体（TrILs），并对其进行了表征以确认组成和离子相互作用。进行了体外药物释放研究和皮肤渗透试验，以评估含有 TrILs 的制剂的性能。
摩尔比为 2:1 的胆碱和 Tr 形成的 TrIL（2[Ch][Tr]）具有突出的溶解度、稳定性和渗透性。与不溶性的 Tr 相比，2[Ch][Tr]即使稀释至 14%仍呈现为澄清透明的水溶液。2[Ch][Tr]的水溶液表现出更好的渗透效果，其中 20%的 2[Ch][Tr]溶液在表皮（2.09±0.18‰）和真皮（3.31±0.48‰）中显示出最佳的传递效率，实现了 API 渗透性的提高。同时，TrILs 可以很容易地制成作为经皮制剂的 o/w 乳剂。乳剂也能够提高 Tr 的皮肤渗透性，但其增强效果不如 TrILs 溶液。
离子液体技术可用于提高 Tr 的溶解度和渗透性，为开发局部制剂和药物的理想经皮应用提供了一种有前途的策略。
