Abstract
Pharmaceutical solid dispersions (SD) of curcumin (Cur) with macromolecule polysaccharide arabinogalactan (AG) from wood of Larix sibirica were prepared by mechanical ball milling. The physical properties of the dispersed curcumin mixture in solid state were characterized by scanning electron microscope, differential scanning calorimetry and powder X-ray diffraction studies. These methods showed a strong decrease in the degree of crystallinity of Cur and its transformation to amorphization state, accompanied by the formation of the guest-host type complexes. The behavior of the samples in solutions was characterized by reverse phase HPLC, 1H NMR spectroscopy, UV-Visible spectroscopy and gel permeation chromatography (GPC). Mechanochemically prepared complexes demonstrated the increased solubility of Cur up to ~10.5 times in contrast to pure curcumin. The rapid storage test showed high chemical stability of Cur, which depended on mass relations of Cur-AG. Besides, improved membrane permeability of Cur-AG SD was tested by parallel artificial membrane permeability assay. Pharmacokinetic study of Cur-AG SD formulation in rat demonstrated a significant~8-fold enhancement of bioavailability in comparison to pure curcumin. In MTT tests, Cur-AG SD showed moderate cytotoxicity against human glioblastoma cells and immortalized human fibroblasts. Therefore, Cur-AG solid dispersion was a more promising and efficacious formulation for application in oral drug delivery.
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