Journal Articles International Journal of Pharmaceutics Year : 2024

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

Extrusion a chaud à haute dose d'un mélange de Luméfantrine amorphe et de soluplus

Shu Li
  • Function : Author
Zi’an Zhang
  • Function : Author
Wenjie Gu
  • Function : Author
Maël Gallas
  • Function : Author
David Jones
  • Function : Author
Lindsay M Johnson
  • Function : Author
Victoire de Margerie
  • Function : Author
Gavin P Andrews
  • Function : Author
  • PersonId : 1433214

Abstract

Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects.

No file

Dates and versions

hal-04755675 , version 1 (03-02-2025)

Identifiers

Cite

Shu Li, Zi’an Zhang, Wenjie Gu, Maël Gallas, David Jones, et al.. Hot Melt Extruded High-Dose Amorphous Solid Dispersions Containing Lumefantrine and Soluplus. International Journal of Pharmaceutics, 2024, 665, ⟨10.1016/j.ijpharm.2024.124676⟩. ⟨hal-04755675⟩
1 View
1 Download

Altmetric

Share

More