Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Eur J Pharm Sci. 2018 Jul 1;119:13-21. doi: 10.1016/j.ejps.2018.03.033. Epub 2018 Apr 3.
Although interactions between drugs and acrylate pressure sensitive adhesives (PSAs) containing amide groups were reported in the previous studies, detailed studies elucidating their mechanism of action are still lacking. In the present study, an amide PSA (AACONH) and a hydroxyl PSA (AAOH, as the control) were synthesized, and their molecular mechanism of controlled drug release was described. Using zolmitriptan (ZOL) and etodolac (ETO) as model drugs, in vitro drug release and skin permeation experiments were performed. Intermolecular interactions between drugs and PSAs were determined by Flory-Huggins model, FT-IR spectroscopic analysis and molecular modeling. In addition, PSA mobility was evaluated using differential scanning calorimetry and rheology study. Release percent of ZOL and ETO from AACONH were 43.9 ± 0.3% and 50.0 ± 2.0% respectively, while from AAOH, the release percent of ZOL and ETO were 61.4 ± 1.2% and 81.0 ± 1.2% separately. As a consequence of controlled drug release, skin permeation of both drugs was significantly controlled by AACONH. It was demonstrated that AACONH markedly interacted with drugs, especially with ETO, through hydrogen bonding and weak intermolecular forces (e.g. dipole-dipole and van der waals). PSA mobility of AACONH was significantly increased due to drug-PSA interactions. In conclusion, AACONH had stronger controlled release properties compared with AAOH, which was mainly caused by the stronger interactions between amide groups and drugs. The amide PSA synthesized in the present study was a potential sustained-release excipient for transdermal drug delivery system.
虽然以前的研究报道了药物与含酰胺基团的丙烯酸盐压敏胶（PSA）之间的相互作用，但详细阐明其作用机制的研究仍然缺乏。在本研究中，合成了一种酰胺 PSA（AACONH）和一种羟基 PSA（AAOH，作为对照），并描述了其控制药物释放的分子机制。使用佐米曲普坦（ZOL）和依托度酸（ETO）作为模型药物，进行了体外药物释放和皮肤渗透实验。通过 Flory-Huggins 模型、FT-IR 光谱分析和分子模拟确定了药物与 PSA 之间的分子间相互作用。此外，还通过差示扫描量热法和流变学研究评估了 PSA 的迁移率。ZOL 和 ETO 从 AACONH 的释放百分比分别为 43.9±0.3%和 50.0±2.0%，而从 AAOH 中，ZOL 和 ETO 的释放百分比分别为 61.4±1.2%和 81.0±1.2%。由于药物的控制释放，两种药物的皮肤渗透都被 AACONH 显著控制。结果表明，AACONH 通过氢键和弱分子间力（如偶极-偶极和范德华力）与药物，特别是 ETO，发生明显相互作用。由于药物与 PSA 的相互作用，AACONH 的 PSA 迁移率显著增加。综上所述，与 AAOH 相比，AACONH 具有更强的控制释放性能，这主要是由于酰胺基团与药物之间更强的相互作用所致。本研究合成的酰胺 PSA 是一种潜在的用于透皮给药系统的持续释放赋形剂。
