چکیده (انگلیسی):

Artemether (ARM) is a poorly water soluble and poorly permeable drug effective against acute
and severe falciparum malaria, hence there is a strong need to improve its solubility. The
objective of the study was to enhance the solubility and dissolution rate of ARM by preparation
of solid dispersions using spray-drying technique. Solid dispersions of ARM were
prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2,
1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy,
differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) to identify
the physicochemical interaction between drug and carrier, as well as effect on dissolution.
The prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared
to neat ARM, which was confirmed by DSC and XRD. Drug/polymer interactions were
studied in-silico by docking and molecular dynamics which indicated formation of van der
Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum
drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation SD3 showed
highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The
spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and
were stable over a period according to ICH guidelines. These findings suggest that an amorphous
solid dispersion of ARM could be a viable option for enhancing the dissolution rate
of ARM.