Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes

Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes Full article

Journal

International Journal of Pharmaceutics
ISSN: 0378-5173 , E-ISSN: 1873-3476

Output data

Year: 2017, Volume: 534, Number: 1-2, Pages: 108-118 Pages count : 11 DOI: 10.1016/j.ijpharm.2017.10.011

Tags

Mechanochemistry; Pharmacokinetics; Simvastatin; Solubility; Supramolecular complexes

Authors

Kong R. ¹ , Zhu X. ¹ , Meteleva E.S. ² , Chistyachenko Y.S. ² , Suntsova L.P. ² , Polyakov N.E. ³ , Khvostov M.V. ⁴ , Baev D.S. ^4,5 , Tolstikova T.G. ⁴ , Yu J. ¹ , Dushkin A.V. ^1,2 , Su W. ¹

Affiliations

1	(Scopus) Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
2	(Scopus) Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russian Federation
3	(Scopus) Institute of Chemical Kinetics and Combustion, Novosibirsk, Russian Federation
4	(Scopus) N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, Novosibirsk, Russian Federation
5	(Scopus) Novosibirsk State University, Novosibirsk, Russian Federation

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. © 2017 Elsevier B.V.

Kong R. , Zhu X. , Meteleva E.S. , Chistyachenko Y.S. , Suntsova L.P. , Polyakov N.E. , Khvostov M.V. , Baev D.S. , Tolstikova T.G. , Yu J. , Dushkin A.V. , Su W.
Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes
International Journal of Pharmaceutics. 2017. V.534. N1-2. P.108-118. DOI: 10.1016/j.ijpharm.2017.10.011 WOS Scopus РИНЦ

Published print:

Dec 1, 2017

Web of science	WOS:000415579600012
Scopus	2-s2.0-85031112386
Elibrary	31065893
OpenAlex	W2761477559