Abstract：
The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe3+). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC0-t and Cmax of the optimized patch were 1045 ± 89 ng/mL·h and 106.8 ± 28.5 ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications.
摘要：
这项研究的目的是设计一种具有良好渗透行为和机械性能的妥洛特罗（TUL）贴片。特别注意经皮渗透促进剂对基于金属配体的丙烯酸压敏粘合剂（AA-NAT/Fe3）的释放过程的影响。通过在大鼠皮肤中的体外透皮渗透来筛选增强剂的类型和剂量。在大鼠的药代动力学研究中评估优化的制剂。此外，通过FT-IR研究了AZ（AZ）提高TUL从AA-NAT/Fe3释放速率的分子机制，剪切强度试验,流变学研究，和分子模拟。因此,与商业产品相比，使用AA-NAT/Fe3+的优化配方显示出更好的机械性能。同时,优化贴剂的AUC0-t和Cmax分别为1045±89ng/mL·h和106.8±28.5ng/mL，分别,这与商业产品没有显著差异。此外,AZ增加了压敏粘合剂（PSA）的流动性，而不是减少药物-PSA的相互作用，这是增强TUL从贴剂释放的主要因素。总之,使用金属配位PSA成功开发了TUL透皮给药贴剂，并为设计用于透皮贴剂的金属配位丙烯酸PSA提供了参考。
