Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Eur J Pharm Sci. 2018 Mar 30;115:330-338. doi: 10.1016/j.ejps.2018.01.038.
Acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system (TDDS). However, there was little research about the quantitative relationship between drug release and drug-PSAs interaction. In this study, five acrylic PSAs with different molar fraction of carboxyl group were designed and synthesized. Propranolol (PRO) was used as model drug to evaluate release profiles in the PSAs in vitro and in vivo. The drug release percent in the PSAs were 81.66, 78.22, 51.66, 21.81 and 11.73%, and their release behaviors were decreased with carboxyl group content of PSAs. Furthermore, it was found that quantity of carboxyl group of PSAs was equal to residual drug by the quantitative determination. In addition, the ionic interaction between PRO and PSAs was confirmed by FT-IR and MDSC results qualitatively. Using the FT-IR, MDSC, Flory-Huggins interaction parameters and molecular dynamic simulation, interaction strength between drug and PSAs was determined quantitatively, which demonstrated that the drug release amount decreased linearly with interaction strength. Based on above results, we proposed that the PRO was possibly binding to the carboxyl group of PSAs one-by-one, which provided references for the accurate design of TDDS.
亚克力压敏胶（PSA）广泛应用于经皮给药系统（TDDS）。然而，关于药物释放与药物 PSA 相互作用之间定量关系的研究较少。本研究设计并合成了五种具有不同羧基摩尔分数的亚克力 PSA。以普萘洛尔（PRO）为模型药物，评估了其在 PSA 中的体外和体内释放曲线。PSA 中的药物释放百分比分别为 81.66%、78.22%、51.66%、21.81%和 11.73%，其释放行为随 PSA 中羧基含量的降低而降低。此外，通过定量测定发现 PSA 中的羧基数量与残留药物相等。此外，通过 FT-IR 和 MDSC 结果定性证实了 PRO 和 PSA 之间的离子相互作用。使用 FT-IR、MDSC、Flory-Huggins 相互作用参数和分子动力学模拟定量确定了药物与 PSA 之间的相互作用强度，结果表明药物释放量随相互作用强度线性下降。基于上述结果，我们提出 PRO 可能与 PSA 的羧基逐一结合，这为 TDDS 的精确设计提供了参考。
