药品
透皮
胶粘剂
透皮贴片
化学
药物输送
药代动力学
剂型
药理学
色谱法
有机化学
医学
图层(电子)
作者
Shuai Zhang,Chao Liu,Yilin Song,Jiuheng Ruan,Peng Quan,Liang Fang
标识
DOI:10.1016/j.jconrel.2022.11.058
摘要
Long-acting transdermal drug delivery system (TDDS) requires high drug-loading and drug controlled-release. To simultaneously improve drug-polymer miscibility and realize drug controlled-release, this work aimed to develop a new pressure sensitive adhesive modified with hydroxyphenyl (HP-PSA) by introducing doubly ionic H-bond into drug-PSA interaction. Eight model drugs divided into R3N, R2NH and no N type were chosen to understand the characteristics of the HP-PSA and inner mechanism. The results showed that the doubly ionic H-bond between R3N and R2NH type drugs and HP-PSA, differing from the ionic bond and neutral H-bond, was a reversible and relatively strong interaction. It could significantly enhance their drug-loading by 1.5 to 7 times and control drug release rate to its 1/5 to 1/2 without altering its total release properties, outperforming the commercial Duro-Tak® 87–2510 and Duro-Tak® 87–2852 adhesives. According to the pharmacokinetics results, the high drug-loading patches based on HP-PSA achieved a sustainable plasma drug concentration avoiding burst release, and over 2 times area under concentration-time curve (AUC) as well as 6 times mean residence time (MRT) revealed its potential to realize long-acting drug delivery. Additionally, its safety and mechanical features were satisfied. The mechanism study showed that the repulsion of the ionic drugs in HP-PSA increased drug-loading, and the relatively strong interaction could also control drug release. The incomplete H-bond transfer determined its reversibility, thus making the drug release percentage up to that of non-functional PSA. In conclusion, the high drug-loading efficiency and drug controlled-release capacity of HP-PSA, as well as its unique interaction, would contribute to the development of TDDS. Moreover, the construction of the doubly ionic H-bond would provide further inspiration for various drug delivery systems in the non-polar environment.
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