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

• Published in: International journal of nanomedicine 2021-01, Vol.16, p.5797-5810
• Main Authors: Kim, Jung Suk, Din, Fakhar Ud, Lee, Sang Min, Kim, Dong Shik, Woo, Mi Ran, Cheon, Seunghyun, Ji, Sang Hun, Kim, Jong Oh, Youn, Yu Seok, Oh, Kyung Taek, Lim, Soo-Jeong, Jin, Sung Giu, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Administration, Oral; Alcohol industry; amorphous microspheres; aqueous microenvironment; Aqueous solutions; Bioavailability; Biological Availability; Cellulose; Comparative analysis; crystalline microspheres; Drug Delivery Systems; Drugs; Emulsions; Microspheres; Mineral oils; Nanoemulsions; Nanoparticles; oral bioavailability; Original Research; Particle Size; Pharmaceutical industry; Pharmacokinetics; Polymers; Polyvinyl alcohol; Povidone; Sildenafil; Sildenafil Citrate; solid self-nanoemulsifying drug delivery system; Solids; Solubility; Solvents; Surfactants; Vehicles; Water
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S324206

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. 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. 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). Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.