Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes

Ruiping Kong, Xingyi Zhu, Elizaveta S. Meteleva, Yulia S. Chistyachenko, Lyubov P. Suntsova, Nikolay E. Polyakov, Mikhail V. Khvostov, Dmitry S. Baev, Tatjana G. Tolstikova, Jianming Yu, Alexander V. Dushkin, Weike Su

    Research output: Contribution to journalArticlepeer-review

    48 Citations (Scopus)

    Abstract

    In the present work, complexes of simvastatin (SIM) with polysaccharide arabinogalactan (AG) or disodium salt of glycyrrhizin acid (Na2GA) have been prepared using mechanochemical technique to improve the solubility of SIM and enhance its oral bioavailability. The interactions of SIM with AG or Na2GA were investigated by FTIR, DSC, XRD and SEM. Self-association of SIM in various solvents was investigated by UV/Vis and NMR techniques. The molecular masses of supramolecular systems–inclusion complexes and micelles, which are the “hosts” for SIM molecules were measured. The parallel artificial membrane permeability assay (PAMPA) revealed a strong increasing of SIM permeability in the presence of Na2GA in comparison with pure SIM used as a control. On the other hand, the rapid storage assay (+40 °C for 3 months) showed that the chemical stability of SIM/AG complexes was similar to pure SIM, but SIM/Na2GA complexes had an enhanced stability. Pharmacokinetic tests in vivo on laboratory animals showed a significant increase in SIM's bioavailability after its introduction as a complex with Na2GA or AG. Moreover, SIM/AG inclusion complex performed better than SIM in reducing total cholesterol level. Therefore, the mechanochemically synthesized complexes of SIM with AG or Na2GA might have a promising future as novel formulations for hyper-cholesterolemia treatment.

    Original languageEnglish
    Pages (from-to)108-118
    Number of pages11
    JournalInternational Journal of Pharmaceutics
    Volume534
    Issue number1-2
    DOIs
    Publication statusPublished - 20 Dec 2017

    Keywords

    • Mechanochemistry
    • Pharmacokinetics
    • Simvastatin
    • Solubility
    • Supramolecular complexes
    • DRUG-DELIVERY-SYSTEM
    • PERMEABILITY
    • SOLUBLE INTERMOLECULAR COMPLEXES
    • GLYCYRRHIZIC ACID
    • SOLID DISPERSIONS
    • BETA-CYCLODEXTRIN
    • ARTIFICIAL MEMBRANE
    • DISSOLUTION RATE
    • POLYSACCHARIDE ARABINOGALACTAN
    • INCLUSION COMPLEX
    • Glycyrrhizic Acid/chemistry
    • Biological Availability
    • Male
    • Drug Carriers/chemistry
    • Micelles
    • Galactans/chemistry
    • Administration, Oral
    • Solvents/chemistry
    • Simvastatin/chemistry
    • Polysaccharides/chemistry
    • Permeability/drug effects
    • Animals
    • Solubility/drug effects
    • Mice

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