Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity

Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 3(2) factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X-1) and sonication time (X-2) on the responses for dependent variables, particle size (Y-1) and time to 90% release of LUF (t(90)) (Y-2). Optimized formulation (F3) has shown to possess lowest particle size (95.34 nm) with minimum t(90) value (square 3 mins), which was lyophilized to obtain the dry powder form of the nanosuspension. The characterization parameters confirmed the amorphous form of LUF with good stability and no chemical interactions of the drug with the incorporated components. Further, saturation solubility study revealed increased solubility of the LUF nanosuspension (1670 mu g/mL) when compared to the pure drug (212.33 mu g/mL). Further, rate of dissolution of LUF from the nanosuspension formulations were found to be significantly (p < 0.05) higher when compared to the pure drug. Fabricated lyophilized nanosuspension was found to be stable at 25 +/- 2 degrees C/60 +/- 5% RH and 40 +/- 2 degrees C/75 +/- 5% RH for the duration of three months. In conclusion, lyophilized nanosuspension showed similar to 8-folds increase in drug release, which indicated a better way to offer higher release of LUF in controlling malaria. [GRAPHICS] .

Automated summary

Lyophilized nanosuspensions of lumefantrine were formulated to improve its low oral bioavailability, showing increased solubility and release rate compared to pure drug. The optimized formulation exhibited stable characteristics and a potential for better malaria control by offering higher release of lumefantrine.