Alamoudi Abdullah A, Ahmed Osama A A, El-Say Khalid M
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceutics. 2021 May 17;13(5):739. doi: 10.3390/pharmaceutics13050739.
To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box-Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X), the concentration of mixed micelles (MMs) in the film (X), and the concentration of the permeation enhancer (X). The initial permeation of AVA after 1 h (Y), and the cumulative permeation of AVA after 24 h (Y) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug's permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase ( < 0.05) in the C of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA.
为避免阿伐那非（AVA）口服给药后的首过代谢及其在食物存在下吸收的改变，本研究旨在研究基于聚乙二醇化维生素E琥珀酸酯（TPGS）的混合胶束（MM）负载膜用于透皮给药及提高生物利用度的潜力。采用Box-Behnken设计优化AVA从透皮膜透过皮肤的渗透行为。变量为表面活性剂的亲水亲油平衡（HLB）（X）、膜中混合胶束（MMs）的浓度（X）和渗透促进剂的浓度（X）。1小时后AVA的初始渗透率（Y）和24小时后AVA的累积渗透率（Y）为因变量。在新鲜分离的大鼠皮肤上进行离体研究，以研究药物的渗透潜力，并使用荧光激光显微镜观察结果。此外，与载有原料药AVA的膜相比，评估了在雄性Wistar大鼠单次给药后的药代动力学行为。结果表明，所用表面活性剂的HLB最佳因子水平为9.4%，膜中MMs为5.12%，渗透促进剂为2.
