Characterization of solid lipid dispersions prepared by hot fusion containing a double-fixed dose combination of artemether and lumefantrine

Abstract

bjective The World Health Organization has called for the development of novel drug delivery systems to combat malaria – the fourth most prevalent cause of death globally. The plausibility of utilizing hot fusion to prepare solid lipid dispersions containing the prescribed first-line, double-fixed dose combination (artemether and lumefantrine), proposed for inclusion in directly compressed lipid matrix tablets, was investigated.

Significance: Currently, no anti-malarial product is commercially available that employs lipid technology in a solid oral dosage form that contains this double-fixed dose combination. Through developing lipid matrix tablets, the stability, solubility and subsequent bioavailability of these drugs could be significantly enhanced in the presence of lipids or oils.

Methods Hot fusion encompasses encompassed melt mixing of a selected lipid base and the dispersion of the active ingredient(s) therein below their glass transition temperatures. Solid-state characterization, particle size analysis and pharmacotechnical properties were evaluated, with particular focus given to powder flowability.

Results Stearic acid in a 0.5:1 lipid:drug ratio demonstrated the best powder flow properties of the investigated solid lipid dispersion for inclusion into prospective lipid–matrix tablets duly based on an increase in overall particle size, a more spherical particle shape and improved powder flow properties compared to the individual active ingredients.

Conclusion Good powder flow is critical for powders destined for inclusion into tablets – especially when employing direct compression as method of manufacture – in this case, lipid matrix tablets, which have demonstrated huge promise as a prospective dosage form for future use in malarial treatment