Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 534, Issue 1-2, Pages 108-118Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2017.10.011
Keywords
Simvastatin; Mechanochemistry; Solubility; Supramolecular complexes; Pharmacokinetics
Categories
Funding
- Zhejiang Natural Science Foundation of China [LY15E080022]
- Russian Foundation for Basic Research [15-04-02538]
- [0301-2016-0017]
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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.
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