Drug Discov Ther. 2010;4(3):190-201.

Characterization, thermodynamic parameters and in vivo antimalarial activity of inclusion complexes of artemether.

Chadha R, Gupta S, Shukla G, Jain DS, Singh S


The present study aimed to improve solubility, dissolution and ultimate bioavailability of poorly soluble artemether, an antimalarial drug, by encapsulating it in β-cyclodextrin (β-CD) and its methyl and hydroxylpropyl derivatives. The effect of these complexes was confirmed by in vivo studies. Phase solubility studies indicated 1:1 stoichiometry and were supported by mass spectrometry and proton nuclear magnetic resonance (1H-NMR) spectroscopy. True inclusion of artemether into the cyclodextrin cavity was observed in lyophilized complexes by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) studies. The mode of inclusion was supported by two-dimensional (2D) NMR. Solution calorimetry was used to confirm 1:1 stiochiometry by determining the enthalpy of interaction between the drug and cyclodextrins. The stability constant (K) of inclusion and other thermodynamic parameters such as enthalpy (ΔH) as well as entropy (ΔS) of binding accompanying the encapsulation were determined. The calculated value of K indicated that M-β-CD has maximum complexing efficiency. Dissolution studies indicated that the highest release rate was observed for lyophilized complexes. In vivo studies of lyophilized complexes of M-β-CD showed a 3-fold increase in antimalarial activity compared to artemether and resulted in 100% eradication of parasite. However, 83% and 50% survival rates were achieved in 40 days using HP-β-CD and β-CD complexes respectively. The study concludes that encapsulation of artemether by cyclodextrins is a good alternative to enhance the bioavailability of the drug.

KEYWORDS: Artemether, β-cyclodextrins, inclusion complex, stoichiometry, in vivo studies

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