Quality-by-design Optimization and Characterization of Artemether–Lumefantrine–Paracetamol Co-loaded Solid Lipid Nanoparticles for Synchronized and Sustained Drug Release
Alphonce Manyoni
Department of Mathematics and Physical Science, Maasai Mara University, P.O. Box 861-20500, Narok, Kenya.
John K. Muchonjo
Department of Public Health, Pharmacology and Toxicology, University of Nairobi, P.O Box 29053-00625, Kangemi, Kenya.
Mpho P. Ngoepe
DSI-Mandela Nanomedicine Platform, Faculty of Health Sciences, Nelson Mandela University, South Africa, Gqeberha 6001, Eastern Cape, South Africa.
Samuel Cheruiyot
Department of Mathematics and Physical Science, Maasai Mara University, P.O. Box 861-20500, Narok, Kenya.
James Owuor
Department of Chemistry and Materials Science Technical University of Kenya, P.O Box, 52428-00100, Nairobi, Kenya.
Evans Suter
Department of Mathematics and Physical Science, Maasai Mara University, P.O. Box 861-20500, Narok, Kenya.
Simon Muigai
Quality Control and Assurance, Lab and Allied Company, P.O Box 42875, Mombasa Road, Nairobi, Kenya.
Wesley Omwoyo
*
Department of Mathematics and Physical Science, Maasai Mara University, P.O. Box 861-20500, Narok, Kenya and DSI-Mandela Nanomedicine Platform, Faculty of Health Sciences, Nelson Mandela University, South Africa, Gqeberha 6001, Eastern Cape, South Africa.
*Author to whom correspondence should be addressed.
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-by-Design (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 polydispersity index (PDI) of 0.136, and a zeta potential of −49.4 mV. Encapsulation 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.
Keywords: Solid lipid nanoparticles, artemether, lumefantrine, paracetamol, malaria, quality by design