Aldawsari Hibah M, Fahmy Usama A, Abd-Allah Fathy, Ahmed Osama A A
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11865, Egypt.
Pharmaceutics. 2020 Jun 26;12(6):596. doi: 10.3390/pharmaceutics12060596.
Avanafil (AVA) is a second-generation phosphodiesterase-5 (PDE5) inhibitor. AVA shows high selectivity to penile tissues and fast absorption, but has a bioavailability of about 36%. The aim was to formulate and optimize AVA-biodegradable nanoparticles (NPs) to enhance AVA bioavailability. To assess the impact of variables, the Box-Behnken design was utilized to investigate and optimize the formulation process variables: the AVA:poly (lactic-co-glycolic acid) (PLGA) ratio (/, X1); sonication time (min, X2); and polyvinyl alcohol (PVA) concentration (%, X3). Particle size (nm, Y1) and EE% (%, Y2) were the responses. The optimized NPs were characterized for surface morphology and permeation. Furthermore, a single-oral dose (50 mg AVA) pharmacokinetic investigation on healthy volunteers was carried out. Statistical analysis revealed that all the investigated factors exhibited a significant effect on the particle size. Furthermore, the entrapment efficiency (Y2) was significantly affected by both the AVA:PLGA ratio (X1) and PVA concentration (X3). Pharmacokinetic data showed a significant increase in the area under the curve (1.68 folds) and plasma maximum concentration (1.3-fold) for the AVA NPs when compared with raw AVA. The optimization and formulation of AVA as biodegradable NPs prepared using solvent evaporation (SE) proves a successful way to enhance AVA bioavailability.
阿伐那非（AVA）是第二代磷酸二酯酶-5（PDE5）抑制剂。AVA对阴茎组织具有高选择性且吸收迅速，但生物利用度约为36%。目的是制备并优化AVA可生物降解纳米颗粒（NPs）以提高AVA的生物利用度。为评估各变量的影响，采用Box-Behnken设计来研究并优化制剂工艺变量：AVA与聚乳酸-羟基乙酸共聚物（PLGA）的比例（/，X1）；超声处理时间（分钟，X2）；以及聚乙烯醇（PVA）浓度（%，X3）。粒径（纳米，Y1）和包封率（%，Y2）为响应指标。对优化后的纳米颗粒进行表面形态和渗透特性表征。此外，对健康志愿者进行了单次口服剂量（50毫克AVA）的药代动力学研究。统计分析表明，所有研究因素对粒径均有显著影响。此外，包封率（Y2）受AVA:PLGA比例（X1）和PVA浓度（X3）两者的显著影响。药代动力学数据显示，与原料药AVA相比，AVA纳米颗粒的曲线下面积显著增加（1.68倍），血浆最大浓度增加（1.3倍）。采用溶剂蒸发法（SE）制备的可生物降解AVA纳米颗粒的优化和制剂工艺证明是提高AVA生物利用度的成功方法。
