Hot Melt Extruded High-Dose Amorphous Solid Dispersions Containing Lumefantrine and Soluplus

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Paediatric artemisinin-based combination therapies face challenges with patient compliance and drug dissolution.
• Poor solubility of lumefantrine in gastrointestinal fluids hinders the effectiveness of artemether/lumefantrine combinations.
• Existing formulations require high-fat meals and exhibit variable dissolution.

Purpose of the Study:

• To develop amorphous solid dispersions of lumefantrine using Soluplus® and hot melt extrusion.
• To enhance the dissolution and apparent solubility of lumefantrine.
• To investigate the impact of extrusion parameters on the stability and performance of the dispersions.

Main Methods:

• Manufacturing amorphous solid dispersions of lumefantrine in Soluplus® matrices via hot melt extrusion.
• Investigating drug loading capacity and in-vitro dissolution performance.
• Examining the influence of varying extrusion conditions (temperature, scale) on physical stability.

Main Results:

• Successful creation of amorphous solid dispersions of lumefantrine within Soluplus®.
• Demonstrated improved in-vitro dissolution of lumefantrine from the dispersions.
• Identified the role of extrusion conditions in the stability and performance of supersaturated amorphous solid dispersions.

Conclusions:

• Hot melt extrusion of amorphous solid dispersions is a viable strategy to improve lumefantrine solubility and dissolution.
• Optimized extrusion processes can lead to stable formulations with enhanced drug performance.
• This approach may enable lower drug dosing, reducing the risk of adverse effects in malaria treatment.