Center for Drug Delivery Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta 30341, Georgia.
CFD Research Corporation, 6820 Moquin Drive NW, Huntsville, AL 35806, USA.
Int J Pharm. 2022 Nov 25;628:122271. doi: 10.1016/j.ijpharm.2022.122271. Epub 2022 Oct 8.
Application of drugs on skin with compromised barrier can significantly alter permeation of drugs with the possibility of increased adverse side effects or even toxicity. In this study, we tested in vitro delivery of diclofenac sodium from marketed brand and generic formulations across normal and compromised skin using microneedles and iontophoresis, alone and in combination. Ten tape strips on dermatomed human skin were used to create a compromised skin model, as demonstrated by changes in skin resistance and transepidermal water loss. Histology studies further confirmed creation of a compromised skin barrier. There was no significant difference between brand and generic formulations for delivery of diclofenac sodium into and across normal and compromised skin. Compromised skin showed higher total delivery (µg/sq.cm) of diclofenac sodium for all groups - microneedles (brand: 79.45 ± 8.81, generic: 92.15 ± 8.63), iontophoresis (brand: 233.13 ± 8.32, generic: 242.07 ± 11.17), combination (brand: 186.88 ± 6.76, generic: 193.8 ± 5.69) as compared to intact normal skin for same groups, microneedles (brand: 21.83 ± 1.96, generic: 20.38 ± 0.91), iontophoresis (brand: 149.78 ± 18.43, generic: 145.53 ± 12.61), and combination (brand: 80.97 ± 9.86, generic: 70.76 ± 6.56). These results indicate the effect of barrier integrity on delivery of diclofenac sodium which suggests increased absorption and systemic exposure of the drug across skin with compromised skin barrier.
应用于受损皮肤屏障的药物会显著改变药物的渗透，可能增加不良反应甚至毒性。在这项研究中，我们使用微针和离子电渗法，单独和联合，测试了市售品牌和仿制药制剂在正常和受损皮肤中的体外递药。使用十片去皮人体皮肤胶带条制作了一个受损皮肤模型，如皮肤电阻和经皮水分丢失的变化所证明的那样。组织学研究进一步证实了受损皮肤屏障的创建。在正常和受损皮肤中，品牌和仿制药制剂递药的差异无统计学意义。所有组的微针组（品牌：79.45 ± 8.81，通用：92.15 ± 8.63）、离子电渗组（品牌：233.13 ± 8.32，通用：242.07 ± 11.17）和联合组（品牌：186.88 ± 6.76，通用：193.8 ± 5.69）中，受损皮肤的双氯芬酸钠总递送量（µg/sq.cm）均高于正常皮肤，而微针组（品牌：21.83 ± 1.96，通用：20.38 ± 0.91）、离子电渗组（品牌：149.78 ± 18.43，通用：145.53 ± 12.61）和联合组（品牌：80.97 ± 9.86，通用：70.76 ± 6.56）。这些结果表明，皮肤屏障完整性对双氯芬酸钠递药的影响提示，与完整皮肤相比，受损皮肤屏障的药物吸收和全身暴露增加。
