Improved pharmacokinetic and pharmacodynamic attributes of artemether-lumefantrine-loaded solid SMEDDS for oral administration.

OBJECTIVES

To evaluate the in-vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.

METHODS

Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S-SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice. Haematology, biochemical parameters and histopathology were performed for evaluating safety of formulation. Pharmacokinetic characterization of both drugs was performed after oral administration in rats.

KEY FINDINGS

Optimized solid SMEDDS containing low, medium and high dose were more effective in reducing parasitemia and mortality of mice as compared to marketed tablets containing high dose of these drugs. Single oral administration of solid SMEDDS containing high-dose combination could maintain plasma concentration of lumefantrine above the minimum effective concentration for ≈4 days.

CONCLUSIONS

Solid SMEDDS containing low-, medium- and high-dose combination of artemether and lumefantrine are more effective than marketed tablets.