Sildenafil citrate as oral solid lipid nanoparticles: a novel formula with higher bioavailability and sustained action for treatment of erectile dysfunction

Abstract

Objective: The aim of this study was to prepare sildenafil citrate as solid lipid nanoparticles (SLNs), in order to find an innovative way for alleviating the disadvantages associated with commercially available sildenafil citrate tablets. These limitations include poor solubility and extensive first-pass metabolism, resulting in low (40%) bioavailability and short elimination half-life (4 h).

Methods: SLNs were prepared by hot homogenization followed by ultrasonication. Solubility of sildenafil citrate in different solid lipids was measured, effect of process variables as surfactant type and concentration, homogenization time, ultrasonication time and charge-inducing agent on the particle size, zeta potential and encapsulation efficiency were also determined. Furthermore, in vitro drug release, stability and in vivo pharmacokinetics were studied in rabbits

Results: The best SLN formula consisted of 2% precirol ATO5, 0.5% phosphatidylcholine, 2.5% gelucire 44/14, 0.125% stearylamine, had an average particle size of 28.5 nm with 95.34% entrapment efficiency and demonstrated a controlled drug release over 24 h. An in vivo pharmacokinetic study revealed enhanced bioavailability by > 1.87 fold, and the mean residence time was longer than that for the commercially available tablet.

Conclusion: SLN could be a promising carrier for sustained/prolonged sildenafil citrate release with enhanced oral bioavailability.

Keywords::

• erectile dysfunction
• gelucire 44/14
• precirol ATO5
• sildenafil citrate
• solid lipid nanoparticles

Acknowledgments

This work was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant no. 166-133-D1435. The authors, therefore, acknowledge with thanks DSR technical and financial support.

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