Abstract：
Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of \"dark ring\", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.
摘要：
经皮给药系统(TDDS)中压敏粘合剂(PSA)的常见问题是皮肤粘附力和机械性能差。其差的水相容性还导致贴片在出汗或浸泡在施用部位后脱落。为了解决这个问题,聚（丙烯酸2-乙基己酯-co-N-乙烯基-2-吡咯烷酮-co-N-（2-羟乙基）丙烯酰胺）（PENH），交联吡咯烷酮聚丙烯酸酯PSA，旨在通过静电力和氢键体系提高PSA的附着力和耐水性。PENH的结构经1HNMR表征,FTIR,DSC,和其他方法。通过FTIR对机理进行了研究,流变试验,和分子模拟。结果表明，PENH贴剂可在人体皮肤上粘附10天以上，无冷流，出汗或水接触后仍然可以粘附。相比之下,商用PSADuro-Tak®87-4098和Duro-Tak®87-2852在第3天和第6天完全脱落，分别,和Duro-Tak®87-2510在第二天显示出明显的暗环。机理研究表明,丙烯酸2-乙基己酯(2-EHA)形成的氢键,N-乙烯基-2-吡咯烷酮(NVP),和N-（2-羟乙基）丙烯酰胺（HEAA）增强内聚力，与皮肤的相互作用改善了皮肤的附着力，与水或药物分子的静电相互作用增强了吸水能力和载药能力。由于氢键和静电力的协同作用，PENH在载药或吸水后可保持较高的内聚力。PENH为开发具有持久粘附力的水相容性贴剂提供了选择。重要性声明：基于氢键和静电力的协同作用，氢键，设计并合成了交联吡咯烷酮丙烯酸酯透皮给药压敏胶,具有高附着力和内聚强度，对皮肤无刺激。贴剂可在皮肤表面连续涂抹10天以上，无“暗环”现象，并且在患者出汗或沐浴后，贴片可以保持粘附性。这为选择需要延长给药的贴剂的基质提供了良好的策略。
