Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 16, Issue -, Pages 5797-5810Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S324206
Keywords
sildenafil; amorphous microspheres; crystalline microspheres; solid self-nanoemulsifying drug delivery system; aqueous microenvironment; oral bioavailability
Funding
- National Research Foundation of South Korea (NRF) - South Korea government (MEST) [2018R1A2B2004668, 2020R1C1C1009663]
- National Research Foundation of Korea [2020R1C1C1009663] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
The study aimed to improve the aqueous solubility and oral bioavailability of sildenafil through various drug delivery systems. Results showed that solid SNEDDS demonstrated the highest enhancement in oral bioavailability compared to amorphous microspheres and crystalline microspheres, making it a recommended oral dosage form for sildenafil.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available