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

Abstract

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 (NaGA) as carriers of drug delivery systems for improving its bioavailability. The interactions of ATV with AG or NaGA 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 °C for 3 months) showed that the chemical stability of ATV/AG and ATV/NaGA 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 NaGA or AG. Pharmacokinetic tests in vivo on laboratory animals showed a significant increase in ATV's bioavailability after its introduction as a complex with NaGA or AG. Moreover, ATV/AG and ATV/NaGA 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 NaGA as drug delivery systems might be potential and promising candidates for hypercholesterolemia treatment and deserved further researches.