Atorvastatin calcium inclusion complexation with polysaccharide arabinogalactan and saponin disodium glycyrrhizate for increasing of solubility and bioavailability

作者：Kong, Ruiping; Zhu, Xingyi; Meteleva, Elizaveta S.; Polyakov, Nikolay E.; Khvostov, Mikhail V.; Baev, Dmitry S.; Tolstikova, Tatjana G.; Dushkin, Alexander V.^*; Su, Weike^*

来源：Drug Delivery and Translational Research, 2018, 8(5): 1200-1213.

DOI：10.1007/s13346-018-0565-x

• Atorvastatin calcium
• Mechanochemistry
• Solubility
• Supramolecular complexes
• Arabinogalactan
• Disodium glycyrrhizin

The aim of the present investigation was to enhance the solubility and dissolution of atorvastatin calcium (ATV), a poorly water-soluble drug with larch polysaccharide arabinogalactan (AG) and disodium glycyrrhizate (Na(2)GA) as carriers of drug delivery systems for improving its bioavailability. The interactions of ATV with AG or Na(2)GA were investigated by DSC. XRD, SEM, and NMR techniques. The molecular weights of supramolecular systems-inclusion complexes and micelles-which are the hosts for ATV molecules were measured. On the other hand, the rapid storage assay (+ 40 degrees C for 3 months) showed that the chemical stability of ATV/AG and ATV/Na(2)GA complexes had been enhanced compared with pure ATV. In vitro drug release showed a significant increase in ATV's dissolution rate after formation of a complex with Na(2)GA or AG. Pharmacokinetic tests in vivo on laboratory animals showed a significant increase in ATV's bioavailability after its introduction as a complex with Na(2)GA or AG. Moreover. ATV/AG and ATV/Na(2)GA complexes showed a more prominent decrease of total cholesterol (TC) level compared to net ATV. Therefore, the novel mechanochemically synthesized complexes of ATV with AG or Na(2)GA as drug delivery systems might be potential and promising candidates for hypercholesterolemia treatment and deserved further researches.

• 出版日期2018-10
• 单位浙江工业大学