Abdallah Marwa H, Abu Lila Amr S, El-Nahas Hanan M, Ibrahim Tarek M
Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Hail 81442, Saudi Arabia.
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Gels. 2023 Jun 18;9(6):494. doi: 10.3390/gels9060494.
Transdermal drug delivery has been widely adopted as a plausible alternative to the oral route of administration, especially for drugs with poor systemic bioavailability. The objective of this study was to design and validate a nanoemulsion (NE) system for transdermal administration of the oral hypoglycemic drug glimepiride (GM). The NEs were prepared using peppermint/bergamot oils as the oil phase and tween 80/transcutol P as the surfactant/co-surfactant mixture (S). The formulations were characterized using various parameters such as globule size, zeta potential, surface morphology, in vitro drug release, drug-excipient compatibility studies, and thermodynamic stability. The optimized NE formulation was then incorporated into different gel bases and examined for gel strength, pH, viscosity, and spreadability. The selected drug-loaded nanoemulgel formulation was then screened for ex vivo permeation, skin irritation, and in vivo pharmacokinetics. Characterization studies revealed the spherical shape of NE droplets with an average size of ~80 nm and a zeta potential of -11.8 mV, which indicated good electrokinetic stability of NE. In vitro release studies revealed enhanced drug release from the NE formulation compared to the plain drug. GM-loaded nanoemulgel showed a 7-fold increment in drug transdermal flux compared to plain drug gel. In addition, the GM-loaded nanoemulgel formulation did not elicit any signs of inflammation and/or irritation on the applied skin, suggesting its safety. Most importantly, the in vivo pharmacokinetic study emphasized the potential of nanoemulgel formulation to potentiate the systemic bioavailability of GM, as manifested by a 10-fold rise in the relative bioavailability compared to control gel. Collectively, transdermal NE-based GM gel might represent a promising alternative to oral therapy in the management of diabetes.
经皮给药已被广泛采用，作为口服给药途径的一种可行替代方案，特别是对于全身生物利用度较差的药物。本研究的目的是设计并验证一种用于口服降糖药格列美脲（GM）经皮给药的纳米乳剂（NE）系统。使用薄荷油/佛手柑油作为油相，吐温80/二乙二醇单乙基醚作为表面活性剂/助表面活性剂混合物（S）制备纳米乳剂。通过各种参数对制剂进行表征，如球粒大小、zeta电位、表面形态、体外药物释放、药物-辅料相容性研究和热力学稳定性。然后将优化后的纳米乳剂配方加入不同的凝胶基质中，并检测凝胶强度、pH值、粘度和铺展性。然后对选定的载药纳米乳凝胶配方进行离体渗透、皮肤刺激性和体内药代动力学筛选。表征研究显示纳米乳滴呈球形，平均大小约为80nm，zeta电位为-11.8mV，表明纳米乳具有良好的电动稳定性。体外释放研究表明，与普通药物相比，纳米乳剂配方的药物释放有所增强。载GM的纳米乳凝胶的药物经皮通量比普通药物凝胶增加了7倍。此外，载GM的纳米乳凝胶配方在用药皮肤上未引起任何炎症和/或刺激迹象，表明其安全性。最重要的是，体内药代动力学研究强调了纳米乳凝胶配方增强GM全身生物利用度的潜力，与对照凝胶相比，相对生物利用度提高了10倍。总的来说，基于经皮纳米乳的GM凝胶可能是糖尿病管理中口服治疗的一种有前途的替代方案。
