Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Department of Pharmaceutics and Pharmaceutical Technology, Egyptian Russian University, Cairo, 11829, Egypt.
Drug Deliv Transl Res. 2023 Sep;13(9):2297-2314. doi: 10.1007/s13346-023-01314-x. Epub 2023 Feb 28.
The highly effective phosphodiesterase type 5 inhibitor (avanafil; AVA) is routinely prescribed to treat erectile dysfunction. The drug has poor oral bioavailability and undergoes a significant first-pass metabolism. Therefore, altering AVA's solubility and choosing a different delivery method may boost its effectiveness. Nine different solid dispersion formulations utilizing polyvinylpyrrolidone (PVP) at three different ratios were prepared and characterized. The Box-Behnken design was employed to optimize AVA-buccal tablets. The pre-compression and post-compression characteristics of the tablets were assessed. The mucoadhesion strength of the optimized tablet was investigated using cow buccal mucosal tissue. In vivo performance of the optimized tablets was examined on human volunteers compared to the commercial tablets. PVP K90 at 2:1 drug to polymer ratio showed the highest solubilization capacity. The mucoadhesive polymer type and percentage and the mucopenetration enhancer percentage were significantly affect the mucoadhesion strength, tablet hardness, and the initial and cumulative AVA released from the prepared tablets. The optimized AVA-buccal tablet showed 4.96 folds increase in the mean residence time, higher plasma exposure, and an improvement in the relative bioavailability of AVA by 1076.27% compared with the commercial tablet. Therefore, a successful approach to deal with AVA first-pass metabolism and low bioavailability could be to employ buccal tablets containing a solubility-enhanced form of AVA.
高效的磷酸二酯酶 5 抑制剂（阿伐那非；AVA）通常被开处方用于治疗勃起功能障碍。该药物口服生物利用度差，且经历显著的首过代谢。因此，改变 AVA 的溶解度并选择不同的给药方式可能会提高其疗效。制备了九种不同的利用聚乙烯吡咯烷酮（PVP）以三种不同比例的固体分散体配方，并对其进行了表征。采用 Box-Behnken 设计优化了 AVA 颊片剂。评估了片剂的预压和后压特性。使用牛颊黏膜组织研究了优化片剂的黏膜黏附强度。将优化片剂的体内性能与人志愿者进行了比较，与市售片剂进行了比较。药物与聚合物比为 2:1 的 PVP K90 显示出最高的增溶能力。黏膜黏附聚合物的类型和百分比以及黏膜穿透增强剂的百分比显著影响黏膜黏附强度、片剂硬度以及从制备的片剂中初始和累积 AVA 的释放。与市售片剂相比，优化的 AVA 颊片剂的平均驻留时间增加了 4.96 倍，血浆暴露量更高，AVA 的相对生物利用度提高了 1076.27%。因此，解决 AVA 首过代谢和低生物利用度的成功方法可能是使用含有溶解度增强形式的 AVA 的颊片剂。
