Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Int J Pharm. 2019 Oct 30;570:118657. doi: 10.1016/j.ijpharm.2019.118657. Epub 2019 Sep 3.
Avanafil (AVA) is a recent FDA approved selective phosphodiesterase type 5 inhibitor used for oral treatment of erectile dysfunction. The oral bioavailability of the drug is challenged by its reduced water solubility, considerable presystemic metabolism, and altered absorption in the presence of food. Accordingly, this work aimed to surmount the aforementioned challenges through the development of optimized nanosized AVA invasomes with enhanced transdermal delivery. AVA invasomes were prepared according to a Box-Behnken experimental design to explore the impact of the following formulation factors: phospholipid % (X), ethanol % (X), terpene % (X), and terpene type (X) on vesicle size (Y) and entrapment efficiency (Y). The three numerical variables were used at three levels, while the categorical variable was used at two levels. The optimized formulation with vesicular size of 109.92 nm and entrapment efficiency of 96.98% was incorporated into a hydroxypropyl methyl cellulose-based transdermal film and characterized for its ex vivo permeation behavior and in vivo performance in rats. The optimized AVA invasomal film showed enhanced ex vivo permeation with an enhancement factor of 2.514 and a more than four-fold increase in relative bioavailability compared to the raw AVA film. These results provide insight into the capability of the optimized invasomal film to enhance the transdermal permeation and bioavailability of AVA.
阿伐那非（AVA）是最近获得美国食品和药物管理局批准的一种选择性磷酸二酯酶 5 抑制剂，用于口服治疗勃起功能障碍。该药物的口服生物利用度受到其低水溶性、大量的前体药物代谢以及在食物存在下吸收改变的影响。因此，本工作旨在通过开发优化的纳米 AVA 入侵体来克服上述挑战，以增强经皮递送。根据 Box-Behnken 实验设计制备 AVA 入侵体，以探讨以下制剂因素对囊泡大小（Y）和包封效率（Y）的影响：磷脂百分比（X）、乙醇百分比（X）、萜烯百分比（X）和萜烯类型（X）。三个数值变量使用三个水平，而分类变量使用两个水平。将具有囊泡大小为 109.92nm 和包封效率为 96.98%的优化配方纳入羟丙基甲基纤维素基经皮膜中，并对其体外渗透行为和大鼠体内性能进行表征。与原始 AVA 膜相比，优化的 AVA 入侵体膜显示出增强的体外渗透，增强因子为 2.514，相对生物利用度增加了四倍以上。这些结果提供了对优化的入侵体膜增强 AVA 经皮渗透和生物利用度的能力的深入了解。
