TY - JOUR

T1 - Atorvastatin calcium inclusion complexation with polysaccharide arabinogalactan and saponin disodium glycyrrhizate for increasing of solubility and bioavailability

AU - Kong, Ruiping

AU - Zhu, Xingyi

AU - Meteleva, Elizaveta S.

AU - Polyakov, Nikolay E.

AU - Khvostov, Mikhail V.

AU - Baev, Dmitry S.

AU - Tolstikova, Tatjana G.

AU - Dushkin, Alexander V.

AU - Su, Weike

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Arabinogalactan

KW - Atorvastatin calcium

KW - Disodium glycyrrhizin

KW - Mechanochemistry

KW - Solubility

KW - Supramolecular complexes

KW - ACID MICELLES

KW - ENHANCED BIOAVAILABILITY

KW - MECHANOCHEMICAL PREPARATION

KW - SOLUBLE INTERMOLECULAR COMPLEXES

KW - PHYSICOCHEMICAL PROPERTIES

KW - SOLID DISPERSIONS

KW - ORAL BIOAVAILABILITY

KW - BETA-CYCLODEXTRIN

KW - IN-VIVO EVALUATION

KW - DISSOLUTION RATE

UR - http://www.scopus.com/inward/record.url?scp=85052281627&partnerID=8YFLogxK

U2 - 10.1007/s13346-018-0565-x

DO - 10.1007/s13346-018-0565-x

M3 - Article

C2 - 30039497

AN - SCOPUS:85052281627

VL - 8

SP - 1200

EP - 1213

JO - Drug Delivery and Translational Research

JF - Drug Delivery and Translational Research

SN - 2190-393X

IS - 5

ER -