Background: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared.
Methods: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier.
Results: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL).
Conclusion: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.



中文翻译：

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三种不同水性微环境提高西地那非口服生物利用度的比较：固体自纳米乳化给药系统、无定形微球和结晶微球

背景：本研究的目的是筛选各种药物递送系统，以提高西地那非的水溶性和口服生物利用度。比较了三种代表性技术，即固体自纳米乳化药物递送系统（SNEDDS）、无定形微球和结晶微球。
方法：两种微球系统均含有重量比为 1:1:6 的西地那非:Labrasol:PVP。使用乙醇制造无定形微球，而使用蒸馏水生成结晶微球。液体 SNEDDS 由 sildenafil:Labrasol:Transcutol HP:Captex 300 组成，比例为 1:70:15:15 (w:w:w:w)。SNEDDS 中的固化过程使用 HDK N20 Pharma 作为固体载体进行。
结果：与药物粉末相比，无定形微球呈球形，粒径显着减小。与西地那非粉末相比，结晶微球表面粗糙，粒径差异不大，表明亲水性赋形剂粘附在西地那非晶体上。假设油性液体被吸附到多孔固体载体上，固体 SNEDDS 呈现出光滑的表面。根据理化评价，结晶微球中保持晶态，而在其他制剂中晶态变为无定形。与药物粉末相比，无定形微球、结晶微球和固体 SNEDDS 的溶解度增加了约 79、55、82 倍。而且，所制备的制剂提供了比药物粉末更高的溶出率 (%) 和血浆浓度（性能顺序；固体 SNEDDS ≥ 无定形微球 ≥ 结晶微球 > 药物粉末）。在这些制剂中，固体 SNEDDS 在口服生物利用度方面表现出最高的改善（AUC；1508.78 ± 343.95 h·ng/mL）。
结论：因此，可以推荐固体 SNEDDS 作为口服剂型，以提高西地那非的口服生物利用度。