三种不同水介质环境对提高西地那非口服生物利用度的比较：固体自微乳药物传递系统、无定形微球和结晶微球。

Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres.

机构信息

College of Pharmacy, Hanyang University, Ansan, South Korea.

Department of Pharmacy, Quaid-I-Azam University, Islamabad, Pakistan.

出版信息

Int J Nanomedicine. 2021 Aug 24;16:5797-5810. doi: 10.2147/IJN.S324206. eCollection 2021.

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.

背景

本研究旨在筛选各种药物传递系统，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，即固体自微乳药物传递系统（SNEDDS）、无定形微球和结晶微球。

方法

两种微球系统均含有西地那非：Labrasol：PVP 重量比为 1：1：6。无定形微球采用乙醇制造，而结晶微球则采用蒸馏水制造。液体 SNEDDS 由西地那非：Labrasol：Transcutol HP：Captex 300 以 1：70：15：15（w：w：w：w）的比例组成。SNEDDS 中的固化过程采用 HDK N20 Pharma 作为固体载体进行。

结果

无定形微球呈球形，与药物粉末相比粒径显著减小。结晶微球表面粗糙，与西地那非粉末相比粒径差异不大，表明亲水性赋形剂附着在西地那非晶体上。固体 SNEDDS 表面光滑，推测油状液体被吸附在多孔固体载体上。根据理化评价，结晶微球中保持结晶状态，而其他制剂中的晶体状态变为无定形态。与原料药相比，无定形微球、结晶微球和固体 SNEDDS 的溶解度分别提高了约 79、55、82 倍。此外，与原料药相比，所制备的制剂具有更高的溶解速率（%）和血浆浓度（性能顺序；固体 SNEDDS≥无定形微球≥结晶微球>原料药）。在这些制剂中，固体 SNEDDS 对口服生物利用度的改善最大（AUC；1508.78±343.95 h·ng/mL）。