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

Ruiping Kong; Xingyi Zhu; Elizaveta S Meteleva; Nikolay E Polyakov; Mikhail V Khvostov; Dmitry S Baev; Tatjana G Tolstikova; Alexander V Dushkin; Weike Su

doi:10.1007/s13346-018-0565-x

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

Drug Deliv Transl Res. 2018 Oct;8(5):1200-1213. doi: 10.1007/s13346-018-0565-x.

Authors

Ruiping Kong¹, Xingyi Zhu¹, Elizaveta S Meteleva², Nikolay E Polyakov³, Mikhail V Khvostov^{4

5}, Dmitry S Baev^{4

5}, Tatjana G Tolstikova^{4

5}, Alexander V Dushkin^{6

7}, Weike Su⁸

Affiliations

¹ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
² Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Novosibirsk, Russia, 630128.
³ Institute of Chemical Kinetics and Combustion, SB RAS, Novosibirsk, Russia.
⁴ N.N. Vorozhtsov Institute of Organic Chemistry, SB RAS, Novosibirsk, Russia.
⁵ Novosibirsk State University, Novosibirsk, Russia.
⁶ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China. dushkin@solid.nsc.ru.
⁷ Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Novosibirsk, Russia, 630128. dushkin@solid.nsc.ru.
⁸ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China. pharmlab@zjut.edu.cn.

PMID: 30039497
DOI: 10.1007/s13346-018-0565-x

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 (Na₂GA) as carriers of drug delivery systems for improving its bioavailability. The interactions of ATV with AG or Na₂GA 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/Na₂GA 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 Na₂GA or AG. Pharmacokinetic tests in vivo on laboratory animals showed a significant increase in ATV's bioavailability after its introduction as a complex with Na₂GA or AG. Moreover, ATV/AG and ATV/Na₂GA 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 Na₂GA as drug delivery systems might be potential and promising candidates for hypercholesterolemia treatment and deserved further researches.

Keywords: Arabinogalactan; Atorvastatin calcium; Disodium glycyrrhizin; Mechanochemistry; Solubility; Supramolecular complexes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Atorvastatin / administration & dosage*
Atorvastatin / chemistry
Atorvastatin / pharmacokinetics*
Biological Availability
Disease Models, Animal
Drug Delivery Systems
Drug Liberation
Drug Stability
Galactans / chemistry*
Glycyrrhizic Acid / chemistry*
Hypercholesterolemia / drug therapy*
Male
Molecular Weight
Rats
Saponins
Solubility

Substances

Galactans
Saponins
Glycyrrhizic Acid
Atorvastatin
arabinogalactan

Grants and funding

0301-2016-0017/the state assignment to ISSCM SB RAS/International