(T1030-08-50) Development of Lumefantrine Amorphous Solid Dispersion Using Vertical Hot Melt Extrusion

Purpose: Lumefantrine is a low solubility and fed-state-dependent bioavailability drug recommended by the World Health Organization (WHO) as a first-line treatment against malaria. In children, achieving therapeutic exposure is particularly challenging in fasting conditions or in cases of malnutrition, where dietary fat intake is insufficient to enhance solubility. To address this, our project focuses on the development of child-friendly formulations using vertical hot melt extrusion (VHME) to produce amorphous solid dispersions (ASDs) with better bioavailability. The vertical platform offers a continuous manufacturing alternative that is both scalable and potentially more energy- and cost-efficient.

Methods: Amorphous solid dispersions containing Lumefantrine and Soluplus® were prepared using a vertical twin-screw extruder. Key processing parameters—such as temperature profiles and screw configurations—were optimized to enhance drug loading and physical stability. In order to evaluate feasibility to progress toward the development of pediatric oral tablets, drug-polymer systems were characterized using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Particle size and morphology, Hygroscopicity (DVS), density, powder flow, compactability and solubility in water and simulated gastric fluid.

Results: Lumefantrine is a yellow powder which has a bulk density of 0.47 g/cm³ with  ‘Passable’ flow characteristic and is composed of large irregular particles with a median diameter of 31 µm as measured by laser diffraction at air pressure of 4 bars. Formulations with 25% (A) and 50% (B) (w/w) Lumefantrine with Soluplus were successfully extruded using the Rondol vertical twin-screw platform. The ASD formulations A and B were also comprised of large particles and exhibited good bulk density value of ca. 0.56 g/cm³ and a ‘Good’ flow characteristic with no need for further densification. Overall, Lumefantrine/Soluplus ASDs presented good compaction properties up to 22kp at 2500 lbf. The compaction properties could even be further improved when mixed with microcrystalline cellulose (MCC). Lumefantrine was classified as ‘Non hygroscopic’ and showed no concerning results for the crystal state evaluation and a melting point around 133°C. However, ASD formulation A and B were classified as ‘Hygroscopic’ with an amorphous structure. The XRPD generated under stress conditions also suggested no concerning results for the amorphous material, but they must be handled, processed, and stored under controlled low- humidity conditions (20%RH) and packaged using moisture protective materials. The 25% loading (Formulation A) exhibited significantly improved solubility in both water (up to 25µg/mL) and 0.1N HCl (up to 13.8µg/mL), while the API remained virtually insoluble ( < 1 µg/mL).

Conclusion: These results support the use of Rondol Vertical All-In-One Twin-Screw Extruder to enhance Lumefantrine bioavailability independently of fed-state conditions. Also the physical properties, specifically compactability of the ASD extrudates showed adequate characteristics for the development and manufacturing of oral solid dosage forms.

References: Gallas, M., Boulet, P., & de Margerie, V. (2023). Extrusion for pharma applications: An update. SPE Polymers, 4(1), 16–23.
Li, S., Zhang, Z., Gu, W., Gallas, M., Jones, D., Boulet, P., Johnson, L. M., de Margerie, V., & Andrews, G. P. (2024). Hot melt extruded amorphous solid dispersions containing lumefantrine and Soluplus. International Journal of Pharmaceutics, Article 124676.
Gallas, M., Medjahdi, G., Boulet, P., & de Margerie, V. (2025). Vertical hot‑melt extrusion: The next challenge in innovation. Pharmaceutics, 17(7), Article 939.

Acknowledgements: No study on humans or animals, No conflit of interest.