Abstract:
Malaria treatment continues to face significant challenges due to emerging drug resistance and
pharmacokinetic heterogeneity among artemisinin-based combination therapies. This study reports
the development of a triple-drug solid lipid nanoparticle (SLN) system employing Compritol® 888
ATO as the lipid matrix and Labrafil® M 1944 CS as the surfactant, co-loaded with artemether,
lumefantrine, and paracetamol to achieve synchronized and sustained drug release. A Quality-byDesign (QbD) approach utilizing a Box±Behnken design was applied to optimize formulation
parameters. The optimized formulation, comprising 1,000 mg of lipid, 2.25% surfactant, and a 60-
minute homogenization time, yielded stable and monodisperse nanoparticles with a mean size of
131.8 nm, a pRO\diVSeUViW\ iQde[ (PDI) Rf 0.136, aQd a ]eWa SRWeQWiaO Rf í49.4 PV. EQcaSVXOaWiRQ
efficiencies were 91.4% for artemether, 93.0% for lumefantrine, and 91.0% for paracetamol,
indicating strong entrapment of the drugs within the solid lipid core. In vitro release studies revealed
cumulative drug releases of 90%, 80%, and 85%, respectively, after 72 hours, with mean release
times of 18.3 and 24.1 hours demonstrating effective release synchronization. The developed SLN
system offers a promising strategy for improving therapeutic efficacy, enhancing patient adherence,
and mitigating drug resistance in malaria management.
