The purpose of the present work is to improve the antimalarial activity of arteether through enhancing its solubility subsequently bioavailability by incorporating the drug into the cyclodextrins cavity. The effect of...The purpose of the present work is to improve the antimalarial activity of arteether through enhancing its solubility subsequently bioavailability by incorporating the drug into the cyclodextrins cavity. The effect of hydrophilic polyvinyl propylene (PVP) polymer on the complexation and solubilizing efficiencies of cyclodextrins (CDs) is also elucidated. Inclusion of arteether molecule in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), and in solution state by NMR and solution calorimetry. A 1:1 stoichiometry was proposed by the phase solubility studies both in presence and absence of PVP. The most plausibe mode of inclusion of arteether into the CD cavity is revealed by molecular modeling studies utalizing Fast Rigid Exhaustive Docking acronym. Solution calorimetry was used further to confirm 1:1 stiochiometry in presence or absence of PVP by determining the enthalpy of interaction between the drug and cyclodextrins. The inclusion of drug was found to be exothermic process accompanied by small positive value of entropy (ΔSo). The methylated-β-CD showed the best ability to solublize arteether which is approximately at par with β-CD in the presence of PVP. Better complexation efficiency of β-CD in presence of PVP is also reflected by the higher numerical values of stability constant (K). Compelete eradication of the parasite from the blood and highest anti-malarial pharmacological activity was observed in the complexes of arteether with M-?-CD while 83.7% was observed for ternary complexes of β-CD in presence of PVP.展开更多
The aim of this study was to investigate and characterize different crystal forms of arteether,a rapidly acting,highly potent antimalarial drug for the treatment of acute Plasmodium falciparum malaria.Six different cr...The aim of this study was to investigate and characterize different crystal forms of arteether,a rapidly acting,highly potent antimalarial drug for the treatment of acute Plasmodium falciparum malaria.Six different crystal forms were prepared utilizing various polar and non-polar solvents.Scanning electron microscopy(SEM)revealed differences in the surface characteristics of the six forms from those of a commercial sample.Differential scanning calorimetry(DSC)revealed the absence of a desolvation endotherm indicating that the forms were neither hydrates nor solvates.Powder X-ray diffraction(PXRD)patterns of the forms showed much weaker major peaks than in the commercial sample indicating them to be less crystalline.Solubility and dissolution studies showed that the most amorphous form was the most soluble and possessed the highest antimalarial activity.展开更多
文摘The purpose of the present work is to improve the antimalarial activity of arteether through enhancing its solubility subsequently bioavailability by incorporating the drug into the cyclodextrins cavity. The effect of hydrophilic polyvinyl propylene (PVP) polymer on the complexation and solubilizing efficiencies of cyclodextrins (CDs) is also elucidated. Inclusion of arteether molecule in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), and in solution state by NMR and solution calorimetry. A 1:1 stoichiometry was proposed by the phase solubility studies both in presence and absence of PVP. The most plausibe mode of inclusion of arteether into the CD cavity is revealed by molecular modeling studies utalizing Fast Rigid Exhaustive Docking acronym. Solution calorimetry was used further to confirm 1:1 stiochiometry in presence or absence of PVP by determining the enthalpy of interaction between the drug and cyclodextrins. The inclusion of drug was found to be exothermic process accompanied by small positive value of entropy (ΔSo). The methylated-β-CD showed the best ability to solublize arteether which is approximately at par with β-CD in the presence of PVP. Better complexation efficiency of β-CD in presence of PVP is also reflected by the higher numerical values of stability constant (K). Compelete eradication of the parasite from the blood and highest anti-malarial pharmacological activity was observed in the complexes of arteether with M-?-CD while 83.7% was observed for ternary complexes of β-CD in presence of PVP.
基金The authors wish to thank the Indian Council of Medical Research,New Delhi,India,for financial support and the Department of Science and Technology(DST),New Delhi,for assistance with instrumentation.
文摘The aim of this study was to investigate and characterize different crystal forms of arteether,a rapidly acting,highly potent antimalarial drug for the treatment of acute Plasmodium falciparum malaria.Six different crystal forms were prepared utilizing various polar and non-polar solvents.Scanning electron microscopy(SEM)revealed differences in the surface characteristics of the six forms from those of a commercial sample.Differential scanning calorimetry(DSC)revealed the absence of a desolvation endotherm indicating that the forms were neither hydrates nor solvates.Powder X-ray diffraction(PXRD)patterns of the forms showed much weaker major peaks than in the commercial sample indicating them to be less crystalline.Solubility and dissolution studies showed that the most amorphous form was the most soluble and possessed the highest antimalarial activity.
