Abstract
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► Nanopowder formulation of lumefantrine (as nanosuspension) was developed to increase antimalarial efficacy of lumefantrine. ► In the present studies, lumefantrine was nano-sized using ‘DYNO MILL’ (wet milling process). Limited reports and literature is available for nano-sizing using DYNO MILL especially for drugs. ► Influence of formulation variables to obtain nano-sized, stable and redispersible lumefantrine nanopowder were discussed. ► Nano-sized lumefantrine powder and unprocessed lumefantrine powder were compared with respect to in vitro antimalarial activity against Plasmodium falciparum 3D7 strain and in vivo antimalarial activity against P. Yoelii nigeriensis (MDR).
Lumefantrine (LMF) is an antimalarial drug that exhibits poor oral bioavailability, owing to its poor aqueous solubility. To improve its antimalarial activity, nanopowder formulation using DYNO MILL was prepared. Combination of HPMC E3 (4%, w/v) and Tween 80 (2.5%, w/v) as dispersing agents, favored the production of smaller LMF particles with mean size of 0.251μm. LMF nanopowder showed enhanced dissolution rate attributed to nanonization of LMF. The IC50 value of nano-sized LMF was found to be 0.1ng/mL, which was 175-times lower than the IC50 value of unmilled LMF powder (17.5ng/mL) and 42-times lower than the IC50 value of chloroquine (4.2ng/mL). The in vivo antimalarial activity demonstrated an enhanced antimalarial potential of LMF nanopowder against P. Yoelii nigeriensis compared to unmilled drug. Wet-milling using DYNO MILL offers a highly effective approach to produce stable drug nanopowders. Furthermore, LMF nanopowder makes the Coartem® therapy more effective.