Formulation design, in vitro characterizations and anti-malarial investigations of artemether and lumefantrine-entrapped solid lipid microparticles

Abstract

Context: Poor aqueous solubility of artemether and lumefantrine makes it important to seek better ways of enhancing their oral delivery and bioavailability.

Objective: To formulate and carry out in vitro and anti-malarial pharmacodynamic evaluations of solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) of artemether and lumefantrine for oral delivery and improved bioavailability.

Materials and methods: Rational blends of Softisan^®154 and Phospholipon^®90H lipid matrices, and different concentrations of artemether and lumefantrine were used to formulate several batches of SLMs. Drug-free SLMs were also formulated. Morphology, particle size, encapsulation efficiency (EE%) and pH studies were performed. In vitro release studies were performed in alcoholic buffer, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. Anti-malarial pharmacodynamic studies were conducted in mice.

Results: Stable, smooth and spherical particles with sizes ranging from 4.2 ± 0.02 to 9.3 ± 0.8 µm were formed. EE% of 92.2–97.3% and 30.2–84.7% and pH of 3.0 ± 0.02 to 4.9 ± 0.12 and 3.0 ± 0.02 to 5.8 ± 0.05 were obtained for artemether and lumefantrine SLMs, respectively. Release of 100, 88.28 and 75.49%, as well as 63.26, 34.31 and 56.17% were recorded for artemether and lumefantrine in alcoholic buffer, SGF and SIF, respectively. Pharmacodynamic studies indicated very significant (p < 0.05) clearance of parasitaemia in plasmodium-infected mice by the drug-loaded SLMs.

Conclusion: Oral delivery and bioavailability of artemether and lumefantrine could be improved using SRMS-based SLMs.

Keywords:

• Drug delivery
• emulsion congealing
• hot homogenization
• parasitaemia
• Phospholipon®90H
• Softisan®154

Acknowledgements

We thank Phospholipid GmbH, Koln, Germany and BASF AG, Ludwigshafen, Germany for providing samples of Phospholipon^®90H and Softisan^®154, respectively, used in this study.

Disclosure statement

The authors state no conflicts of interest and have received no funding either for the research or in the preparation of this manuscript.