Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Industrial Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.
Int J Pharm. 2020 Jun 15;583:119371. doi: 10.1016/j.ijpharm.2020.119371. Epub 2020 Apr 24.
Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations.
CG4500 (acrylic acid/acrylamide-methyl propane sulfonic acid copolymer) was thiolated by conjugation with L-cysteine and preactivated by further modification with 2-mercaptonicotinic acid (MNA) in a two-step synthesis and characterized regarding degree of modification and cytotoxicity on Caco-2 cells. The mucoadhesive properties of this novel thiomer were evaluated via rheological synergism, tensile and mucosal residence time studies. Furthermore, the sprayability of the thiomer was evaluated.
The newly synthesized derivatives CG4500-SH and CG4500-S-S-MNA showed mean coupling rates of 651 µmol thiol groups and 264 µmol MNA per gram polymer, respectively. Even for the unmodified polymer a rheological synergism was observed with isolated porcine intestinal mucus, which was 2.81-fold higher in case of the preactivated thiomer. Mucoadhesion studies on freshly excised porcine intestinal mucosa confirmed these results via a 2.43-fold higher total work of adhesion and a 2.31-fold higher mucosal residence time of the preactivated thiomer. In sprayability tests it was shown that solutions of the preactivated thiomer could be sprayed in concentrations up to 12% (m/V).
The novel polymer CG4500-S-S-MNA is a promising sprayable excipient for mucoadhesive formulations.
开发一种预激活的硫醇作为可喷雾的黏附制剂赋形剂。
CG4500（丙烯酸/丙烯酰胺-甲基丙烷磺酸共聚物）通过与 L-半胱氨酸缀合进行巯基化，并通过与 2-巯基烟酸（MNA）进一步修饰在两步合成中进行预激活，并对其进行修饰程度和对 Caco-2 细胞的细胞毒性进行表征。通过流变协同作用、拉伸和黏膜停留时间研究评估这种新型硫醇的黏附性能。此外，还评估了硫醇的喷雾性能。
新合成的衍生物 CG4500-SH 和 CG4500-S-S-MNA 的平均偶联率分别为 651µmol 巯基和 264µmol MNA 每克聚合物。即使是未修饰的聚合物，与分离的猪肠黏液也观察到流变协同作用，而预激活的硫醇的协同作用提高了 2.81 倍。对新鲜取出的猪肠黏膜的黏附研究通过预激活硫醇的总黏附功提高了 2.43 倍和黏膜停留时间提高了 2.31 倍证实了这些结果。在喷雾性能测试中，表明预激活硫醇的溶液可以在高达 12%（m/V）的浓度下喷雾。
新型聚合物 CG4500-S-S-MNA 是一种有前途的可喷雾的黏附制剂赋形剂。
