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

ABSTRACT

OBJECTIVE: 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 0.51 lipiddrug 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.