Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes. / Kong, Ruiping; Zhu, Xingyi; Meteleva, Elizaveta S. et al.
In: International Journal of Pharmaceutics, Vol. 534, No. 1-2, 20.12.2017, p. 108-118.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes
AU - Kong, Ruiping
AU - Zhu, Xingyi
AU - Meteleva, Elizaveta S.
AU - Chistyachenko, Yulia S.
AU - Suntsova, Lyubov P.
AU - Polyakov, Nikolay E.
AU - Khvostov, Mikhail V.
AU - Baev, Dmitry S.
AU - Tolstikova, Tatjana G.
AU - Yu, Jianming
AU - Dushkin, Alexander V.
AU - Su, Weike
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/12/20
Y1 - 2017/12/20
N2 - 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.
AB - 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.
KW - Mechanochemistry
KW - Pharmacokinetics
KW - Simvastatin
KW - Solubility
KW - Supramolecular complexes
KW - DRUG-DELIVERY-SYSTEM
KW - PERMEABILITY
KW - SOLUBLE INTERMOLECULAR COMPLEXES
KW - GLYCYRRHIZIC ACID
KW - SOLID DISPERSIONS
KW - BETA-CYCLODEXTRIN
KW - ARTIFICIAL MEMBRANE
KW - DISSOLUTION RATE
KW - POLYSACCHARIDE ARABINOGALACTAN
KW - INCLUSION COMPLEX
KW - Glycyrrhizic Acid/chemistry
KW - Biological Availability
KW - Male
KW - Drug Carriers/chemistry
KW - Micelles
KW - Galactans/chemistry
KW - Administration, Oral
KW - Solvents/chemistry
KW - Simvastatin/chemistry
KW - Polysaccharides/chemistry
KW - Permeability/drug effects
KW - Animals
KW - Solubility/drug effects
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=85031112386&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2017.10.011
DO - 10.1016/j.ijpharm.2017.10.011
M3 - Article
C2 - 28993167
AN - SCOPUS:85031112386
VL - 534
SP - 108
EP - 118
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -
ID: 9429088