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Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation

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Abstract

The interest in hot-melt extrusion as a drug delivery technology for the production of solid dispersion is growing rapidly. Lumefantrine (LUMF) is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared. Appropriate selection of polymers, favoured the production of amorphous LUMF-polymer solid dispersions. The physicochemical properties of solid dispersions were characterized using scanning electron microscope, Infrared spectroscopy, differential scanning calorimetry and X-ray diffraction. LUMF SD showed enhanced dissolution rate attributed to amorphosization of LUMF. The IC50 value of LUMF SD formulations was found to be (0.084–0.213 ng/mL) i.e. 220–101 times lower than the IC50 value of pure LUMF (18.2 ng/mL) and 45–18 times lower than the IC50 value of standard antimalarial drug, chloroquine (3.8 ng/mL). Molecular dynamic simulation approach was used to investigate drug-polymer molecular interaction using computational modelling Schrodinger® software. LUMF SD powder makes the Coartem® therapy more operative with value-added beneficial comeback.

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Acknowledgments

The authors are thankful to Bajaj Healthcare Pvt. Ltd. (India) for providing the gift sample of Lumefantrine, BASF Ltd. Mumbai for the gift sample of Soluplus and Kollidone VA64 and, ISP Ltd. for Plasdone S630. The author is also thankful to UGC (SAP) for providing the research fellowship and Institute of Chemical Technology (Mumbai, India) for providing all facilities and guidance. The author is also thankful to Mr. Pavankumar Todkar from Dept. of Virology and Immunology, Haffkine Institute, Parel, Mumbai for helping with in vitro antimalarial studies at his laboratory.

Conflict of interest

Author declares that we do not have any conflict of interest.

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Correspondence to Ritesh Fule.

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Fule, R., Meer, T., Sav, A. et al. Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation. Journal of Pharmaceutical Investigation 43, 305–321 (2013). https://doi.org/10.1007/s40005-013-0078-z

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Keywords

  • Lumefantrine
  • Hot melt extrusion
  • Solid dispersion
  • Dissolution rate
  • Solubility