Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
AAPS PharmSciTech. 2022 Jan 4;23(1):46. doi: 10.1208/s12249-021-02195-4.
The in vitro dissolution of Avanafil (AVA) is the rate-limiting step for its bioavailability. Also, it undergoes the first-pass metabolism, and its absorption is altered significantly in the presence of food. So, our study aimed to overcome the previous hurdles and improve the AVA bioavailability by its incorporation in the ultra-deformable nanovesicles, transfersomes (TRF), then loading these nanovesicles in transdermal films. The AVA-loaded TRF formulation was optimized using Draper-Lin small composite design (D-LSCD). The optimized AVA-loaded TRF was evaluated for quality attributes and assessed for skin permeation using a fluorescence laser microscope and for pharmacokinetic parameters after topical application on the rats. The optimized AVA-loaded TRF showed a vesicle size of 97.75 nm, a zeta potential of -28.83 mV, and entrapment efficiency of 95.14% with good deformability and release profile. The intense discoloration in the deep skin layers of the rats indicated the permeation efficiency of AVA-loaded TRF films. The pharmacokinetic parameters specified the augmented absorption extent with C of 254.66 ± 8.02 ng/mlversus 70.33 ± 3.05 ng/ml which reflected on the AUC that has a value of 2050.45 ± 159.14 ng/ml h versus 497.34 ± 102.61 ng/ml h for the optimized AVA-loaded TRF film and raw AVA-loaded film, respectively. These promising results wide open the field for broader clinical application of this alternative delivery pathway for superior bioavailability, efficacy, and patient compliance and satisfaction.
阿伐那非（AVA）的体外溶出是其生物利用度的限速步骤。此外，它还经历了首过代谢，并且在存在食物的情况下其吸收会发生明显改变。因此，我们的研究旨在克服以前的障碍，通过将其纳入超变形纳米囊泡（TRF）来提高 AVA 的生物利用度，然后将这些纳米囊泡载入透皮贴剂中。使用 Draper-Lin 小复合设计（D-LSCD）对载 AVA 的 TRF 制剂进行了优化。对载 AVA 的优化 TRF 进行了质量属性评估，并使用荧光激光显微镜评估了其皮肤渗透性能，以及在大鼠上局部应用后的药代动力学参数。载 AVA 的优化 TRF 显示出 97.75nm 的囊泡大小、-28.83mV 的 Zeta 电位和 95.14%的包封效率，具有良好的变形性和释放特性。在大鼠深层皮肤层的强烈变色表明 AVA 载 TRF 膜具有渗透效率。药代动力学参数表明，载 AVA 的 TRF 膜的吸收程度增强，C 值为 254.66±8.02ng/ml，而 70.33±3.05ng/ml 反映了 AUC 的值为 2050.45±159.14ng/ml h，而对于优化的 AVA 载 TRF 膜和载 AVA 的原始膜分别为 497.34±102.61ng/ml h。这些有希望的结果为这一替代给药途径的更广泛临床应用开辟了广阔的前景，以实现更高的生物利用度、疗效、患者依从性和满意度。
