Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes

被引：75

作者：

Kong, Ruiping ^{[1
]}

Zhu, Xingyi ^{[1
]}

Meteleva, Elizaveta S. ^{[2
]}

Chistyachenko, Yulia S. ^{[2
]}

Suntsova, Lyubov P. ^{[2
]}

Polyakov, Nikolay E. ^{[3
]}

Khvostov, Mikhail V. ^{[4
]}

Baev, Dmitry S. ^{[4
,5
]}

Tolstikova, Tatjana G. ^{[4
]}

Yu, Jianming ^{[1
]}

Dushkin, Alexander V. ^{[1
,2
]}

Su, Weike ^{[1
]}

机构：

[1] Zhejiang Univ Technol, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China

[2] Inst Solid State Chem & Mechanochem, Novosibirsk 630128, Russia

[3] Inst Chem Kinet & Combust, Novosibirsk, Russia

[4] NN Vorozhtsov Inst Organ Chem SB RAS, Novosibirsk, Russia

[5] Novosibirsk State Univ, Novosibirsk, Russia

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2017年 / 534卷 / 1-2期

基金：

浙江省自然科学基金; 俄罗斯基础研究基金会;

关键词：

Simvastatin; Mechanochemistry; Solubility; Supramolecular complexes; Pharmacokinetics; SOLUBLE INTERMOLECULAR COMPLEXES; DRUG-DELIVERY-SYSTEM; GLYCYRRHIZIC ACID; POLYSACCHARIDE ARABINOGALACTAN; SOLID DISPERSIONS; BETA-CYCLODEXTRIN; ARTIFICIAL MEMBRANE; INCLUSION COMPLEX; DISSOLUTION RATE; PERMEABILITY;

D O I：

10.1016/j.ijpharm.2017.10.011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In the present work, complexes of simvastatin (SIM) with polysaccharide arabinogalactan (AG) or disodium salt of glycyrrhizin acid (Na(2)GA) have been prepared using mechanochemical technique to improve the solubility of SIM and enhance its oral bioavailability. The interactions of SIM with AG or Na(2)GA 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 Na(2)GA in comparison with pure SIM used as a control. On the other hand, the rapid storage assay (+40 degrees C for 3 months) showed that the chemical stability of SIM/AG complexes was similar to pure SIM, but SIM/Na(2)GA 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 Na(2)GA 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 Na(2)GA might have a promising future as novel formulations for hyper-cholesterolemia treatment.

引用

页码：108 / 118

页数：11

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