Cocrystallization of Artemisinin and Amodiaquine Hydrochloride

Abstract

Artemisinin (ART) and amodiaquinedihydrochloride dihydrate (AQD) was selected

as model host and guest molecules in the study. Cocrystallization of ART and AQD at mole

ratio of 1:1 by temperature change technique using ethanol, new structure was found, Rec-

ART-AQD (1:1), showed distinctively different XRPD pattern from control. However, major

XRPD pattern remained as amodiaquine nonohydrate (AQM). In addition, FT-IR spectrum of

Rec-ART-AQD (1:1) showed the shift in wavenumber from 3440 cm-1 to lower region. This

shift was due to the H-bonding of –NH functional group on AQM interacting with ART.

Thermal analyses of Rec-ART-AQD (1:1) also show lower average endothermic dehydration

energy starting at slightly lower temperature than AQM which correlates well with TGA

results. Rec-ART-AQ (1:1) was analyzed for each component by HPLC. The result shows

that the recrystallized crystal contains 3.50% w/w of ART signifying ART:AQM mole ratio

of 1:16 in the cocrystal. The solubility of ART in Rec-ART-AQ (1:1) at 30°C is 79.87µg/ml

where it was found to be 33.41% higher than the original ART solubility (59.87µg/ml). Rec-

ART-AQ (1:1) was found to have good stability with no observable water uptake under

various humidities generated by dynamic vapor sorption (DVS) apparatus. Rec-ART-AQ

(1:1) shows slight increase in antimalarial activity against P. falciparum. From the above

supporting results, crystals obtained by recrystallization of ART together with AQD are

cocrystals with uniform distribution of individual ART molecule in the major crystalline

lattice of AQM at a mole ratio of 1:16.