Abstract

The aim of the current investigation was to develop solid lipid nanoparticles of olmesartan medoxomil using hot homogenization method to improve its oral bioavailability. Central composite design was applied to optimize the formulation variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween 80). The particle sizes were in the nanometer range and spherical shaped for all prepared solid lipid nanoparticles formulations and the zeta potential absolute values were high, predicting good long-term stability. In vitro study of olmesartan loaded solid lipid nanoparticle exhibited controlled release profile for at least 24 hour. The rate and extent of drug diffusion was studied using dialysis sac, rat’s stomach and intestine tissues; study demonstrated that drug release from the solid lipid nanoparticles was significantly higher than drug suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL and increased relative bioavailability by almost 2.3 folds compared to marketed formulation. These results clearly indicate that olmesartan loaded solid lipid nanoparticles are shown to have enhanced bioavailability and effective therapeutic result and thus would be an excellent way to treat hypertension. Hence, these solid lipid nanoparticles could represent as a great potential for a possible alternative to conventional oral formulation in the treatment of hypertension.

Conclusion

In this study, stable OLM loaded SLNs were formulated using hot homogenization method consisting essentially of glyceryl monostearate (108.94mg) and 1:1 w/w ratio of Poloxamer 407:Tween 80 (1.84%). The results showed that the OLM loaded SLNs were found to be stable; nanometer sized spherical particles, with low PDI and better in vitro release in stimulated fluids. The OLM loaded SLNs following oral administration in rat showed an almost 2.3 fold increase in plasma exposure of the drug. Based on the results, OLM loaded SLNs can provide an alternative to the current available therapy in hypertension by solving the practical problems of poor solubility, low oral absorption and thereby reduced bioavailability. Hence, it can be concluded that the developed OLM loaded SLNs can represent better and effective drug delivery system than conventional drug delivery system in hypertension.

More