Journal of Pharmaceutical Investigation

, Volume 43, Issue 4, pp 305–321 | Cite as

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

  • Ritesh FuleEmail author
  • Tariq Meer
  • Ajay Sav
  • Purnima Amin
Research Article


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.


Lumefantrine Hot melt extrusion Solid dispersion Dissolution rate Solubility 



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.

Supplementary material

Supplementary material 1 (MP4 6826 kb)

40005_2013_78_MOESM2_ESM.xlsx (12 kb)
Supplementary material 2 (XLSX 11 kb)


  1. Almeida A, Possemiers S (2011) Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion. Eur J Pharm Biopharm 77(2):297–305PubMedCrossRefGoogle Scholar
  2. Ambike AA, Mahadik KR, Paradkar A (2004) Stability study of amorphous valdecoxib. Int J Pharm 282:151–162PubMedCrossRefGoogle Scholar
  3. Andriantsoanirina V (2011) Resistance of Plasmodium falciparum to antimalarial drugs: impact on malaria pre-elimination in Madagascar. Med Trop Mars 1:298–304Google Scholar
  4. Bacon DJ, Latour C, Picot S (2007) Comparison of a SYBR green i-based assay with a histidine-rich protein ii enzyme-linked immunosorbent assay for in vitro antimalarial drug efficacy testing and application to clinical isolates. Antimicrob Agents Chemother 51:1172–1178PubMedCrossRefGoogle Scholar
  5. Breitenbach J (2002) Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm 54:107–117Google Scholar
  6. Chiou WL, Riegelman S (1971) Pharmaceutical applications of solid dispersion systems. J Pharm Sci 60:1281–1302PubMedCrossRefGoogle Scholar
  7. Chokshi RJ, Zia H, Sandhu HK, Shah NH, Malick WA (2007) Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution. Drug Deliv 14(1):33–45PubMedCrossRefGoogle Scholar
  8. Crowley MM, Zhang F, Koleng JJ, McGinity JW (2002) Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion. Biomaterials 23:4241–4248PubMedCrossRefGoogle Scholar
  9. Doshi DH, Betageri GV (1997) Carbamazepine and polyethylene glycol solid dispersion preparation, in vitro dissolution, and characterization. Drug Dev Ind Pharm 23:1167–1176CrossRefGoogle Scholar
  10. Ford JL (1986) The current status of solid dispersions. Pharm Acta Helvetica 61:69–88Google Scholar
  11. Gahoia S, Jain GK (2012) Enhanced antimalarial activity of lumefantrine nanopowder prepared by wet-milling DYNO MILL technique. Colloids Surf B Biointerfaces. doi: 10.1016/j.colsurfb.2012.01.047 Google Scholar
  12. Gavin PA, Osama AD (2010) Physicochemical characterization and drug-release properties of celecoxib hot-melt extruded glass solutions. J Pharm Pharmacol 62:1580–1590CrossRefGoogle Scholar
  13. Greenhalgh DJ, Timmins PY (1999) Solubility parameters as predictors of miscibility in solid dispersions. J Pharm Sci 88:1182–1190PubMedCrossRefGoogle Scholar
  14. Hancock BC, Zografi G (1997) Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 86:1–12PubMedCrossRefGoogle Scholar
  15. Higuchi T, Connors K (1965) Phase-solubility techniques. Adv Anal Chem Inst Technol 4:117–130Google Scholar
  16. Juma E (2008) A randomized, open-label, comparative efficacy trial of artemether-lumefantrine suspension versus artemether-lumefantrine tablets for treatment of uncomplicated Plasmodium falciparum malaria in children in western Kenya. Malar J 7:262–280PubMedCrossRefGoogle Scholar
  17. Kalogeras IM (2011) A novel approach for analyzing glass-transition temperature vs. composition patterns: application to pharmaceutical compound+polymer systems. Eur J Pharm Sci 42:470–483PubMedCrossRefGoogle Scholar
  18. Konno H, Taylor LS (2006) Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci 95:2692–2705PubMedCrossRefGoogle Scholar
  19. Linn M (2012) Soluplus as an effective absorption enhancer of poorly soluble drugs in vitro. Eur J Pharm Sci 45:336–343PubMedCrossRefGoogle Scholar
  20. Makar RR, Latif R, Hosni EA, Omaima N, Gazayerly El (2013) Optimization for glimepiride dissolution enhancement utilizing different carriers and techniques. J Pharm Invest 43:115–131CrossRefGoogle Scholar
  21. Maniruzzaman M, Morgan DJ, Douroumis D (2013) Drug–polymer intermolecular interactions in hot-melt extruded solid dispersions. Int J Pharm 443:199–208PubMedCrossRefGoogle Scholar
  22. McGinity JW, Zhang F, Repka MA, Koleng JJ (2001) Hot-melt extrusion as a pharmaceutical process. Am Pharm Rev 4(2):25–36Google Scholar
  23. Osama AA, David SJ (2012) Understanding the performance of melt-extruded poly(ethylene oxide)-bicalutamide solid dispersions: characterisation of microstructural properties using thermal, spectroscopic and drug release methods. J Pharm Sci 101:200–213CrossRefGoogle Scholar
  24. Rasenack N, Muller B (2002) Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution. Arch Pharm Res 19:1894–1903CrossRefGoogle Scholar
  25. Repka MA, Prodduturi S, Stodghill SP (2003) Production and characterization of hot-melt extruded films containing clotrimazole. Drug Dev Ind Pharm 29:757–765PubMedCrossRefGoogle Scholar
  26. Suneela P (2005) Solid-state stability and characterization of hot-melt extruded poly(ethylene oxide) films. J Pharm Sci 94:2232–2245CrossRefGoogle Scholar
  27. Takeuchi H, Nagira S (2004) Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying method. Powder Technol 141:187–195CrossRefGoogle Scholar
  28. Vasconcelos T, Sarmento B, Costa P (2007) Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Disc Today 12:1068–1075CrossRefGoogle Scholar
  29. Zhang F, McGinity JW (1999) Properties of sustained- release tablets prepared by hot-melt extrusion. Pharm Dev Technol 4:241–250PubMedCrossRefGoogle Scholar
  30. Zsombor KN, Attila B (2012) Comparison of electrospun and extruded Soluplus -based solid dosage forms of improved dissolution. J Pharm Sci 101:322–332CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2013

Authors and Affiliations

  • Ritesh Fule
    • 1
    Email author
  • Tariq Meer
    • 1
  • Ajay Sav
    • 1
  • Purnima Amin
    • 1
  1. 1.Department of Pharmaceutical Science and TechnologyInstitute of Chemical TechnologyMumbaiIndia

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