Journal of Thermal Analysis and Calorimetry

, Volume 120, Issue 1, pp 759–769 | Cite as

Evaluation of compatibility among artemether, pyrimethamine and sulphadoxine using analytical and isothermal calorimetry techniques

  • Sushma Gupta
  • Renu Chadha


The objective of the present study is to identify interactions and incompatibilities among antimalarial drugs in solid state and solution phase. The potential interactions can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. Herein, the incompatibility studies were performed on artemether: sulphadoxine/pyrimethamine and their physical and treated binary and ternary mixtures. DSC, FT-IR and PXRD outcomes showed no significant chemical changes in physical mixtures and treated samples with respect to their pure samples. In solid state, no changes in data output (exotherm) was observed during conducting tests in isothermal heat flow among binary and ternary mixtures. In solution phase, more exothermic value of excess energy by calorimetry indicated stronger interaction in ternary mixtures relative to binary mixtures. Current investigation unambiguously connoted that artemether was compatible with pyrimethamine or sulphadoxine in combinations, but their ternary mixtures are not safe if co-formulated.


Artemether Compatibility studies Drug interactions Combinations Calorimetry 



The financial assistance provided by Indian Council of Medical research, New Delhi, India and Instrumentation assistance by Department of Science Technology (DST), New Delhi are acknowledged gratefully.

Conflict of interest

The authors show no conflict of interest.


  1. 1.
    Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how can it be achieved. Nat Rev Microbiol. 2006;4:682–95.CrossRefGoogle Scholar
  2. 2.
    Santos-Magalhães NS, Mosqueira VCF. Nanotechnology applied to the treatment of malaria. Adv Drug Deliv Rev. 2010;62(4–5):560–75.CrossRefGoogle Scholar
  3. 3.
    World Health Organization. Position of WHO’s Roll Back Malaria. Department on malaria treatment policy. WHO Position Statement: 3. 2003:1–4. Available at : Accessed 5 April 2013.
  4. 4.
    Yeung S, Vornpinyo WP, Hastings IM, Anne JM, Nicholas JW. Antimalarial drug resistance, artemisinin-based combination therapy, and the contribution of modeling to elucidating policy choices. Am J Trop Med Hyg. 2004;71(2):179–86.Google Scholar
  5. 5.
    Snow RW, Trape JF, Marsh K. The past, present and future of childhood malaria mortality in Africa. Trends Parasitol. 2001;17:593–7.CrossRefGoogle Scholar
  6. 6.
    Zakeri S, , Afsharpad M, Raeisi A, Djadid ND. Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran. Malar J. 2007;6:148. doi: 10.1186/1475-2875-6-148.CrossRefGoogle Scholar
  7. 7.
    Olliaro PL, Taylor WRJ. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: a review. J Postgrad Med. 2004;50(1):40–4.Google Scholar
  8. 8.
    Meshnick SR, Taylor TE, Kamchonwongpaisan S. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev. 1996;60(2):301–15.Google Scholar
  9. 9.
    Van VM, Brockman A, Gemperli B, Luxemburger C, Gathmann I, Royce C, Slight T, Looareesuwan S, White NJ, Nosten F. Randomized comparison of artemether-benflumetol and artesunate mefloquine in treatment of multidrug-resistant falciparum malaria. Antimicrob Agents Chemother. 1998;42:135–9.Google Scholar
  10. 10.
    Von Seidlein L, Bojang K, Jones P, Jaffar S, Pinder M, Obaro S, Doherty T, Haywood M, Snounou G, Gemperli B, Gathmann I, Royce C, McAdam K, Greenwood B. A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children. Am J Trop Med Hyg. 1998;58:638–44.Google Scholar
  11. 11.
    Mura P, Gratteri P, Faucci MT. Compatibility studies of multicomponent tablet formulations. J Ther Anal Cal. 2002;68:541–51.CrossRefGoogle Scholar
  12. 12.
    Marini A, Berbenni V, Pegoretti M, Bruni G, Cofrancesco P, Sinistri C, Villa M. Drug-excipient compatibility studies by physico-chemical techniques. J Ther Anal Cal. 2003;73:547–61.CrossRefGoogle Scholar
  13. 13.
    Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer. Drug J Biomed Biotechnol. 2012;2012:1–18.CrossRefGoogle Scholar
  14. 14.
    Kakran M, Sahoo NG, Lin Li, Judeh Z. Dissolution enhancement of artemisinin with β-cyclodextrin. Chem Pharm Bull (Tokyo). 2011;59(5):646–52.CrossRefGoogle Scholar
  15. 15.
    Chadha R, Kashid N, Jain DVS. Characterization and quantification of amorphous content in some selected parenteral cephalosporins by calorimetric method. J Ther Anal Cal. 2005;81:277–84.CrossRefGoogle Scholar
  16. 16.
    Chadha R, Kashid N, Jain DVS. Microcalorimetric evaluation of the in vitro compatibility of amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin. J Pharm Biomed Anal. 2004;36:295–307.CrossRefGoogle Scholar
  17. 17.
    Wissing S, Craig DQM. Barker SA, Moore WD. An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibility. Int J Pharm. 2000;199:141–50.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2014

Authors and Affiliations

  1. 1.University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia

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