摘要
Ischemic brain injury is a major disease which threatens human health and safety.(3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate(VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/ polyvinylpyrrolidone(PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry(DSC), infrared spectroscopy(IR), x-ray diffraction(XRD) and scanning electron microscopy(SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1 : 5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.
Ischemic brain injury is a major disease which threatens human health and safety. （3, 5, 6-trimethylpyrazin-2-yl） methyl 3-methoxy-4-[（3, 5, 6-trimethylpyrazin-2-yl） methoxy] benzoate （VA-T）, a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone （PVP） solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry （DSC）, infrared spectroscopy （IR）, x-ray diffraction （XRD） and scanning electron microscopy （SEM）. The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1 ： 5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.
基金
financially supported by National Natural Science Foundation of China(No.81173563)
Ministry of National Science and Technology(China
Nos.2012ZX09103201-026
2009ZX09102-142)
the Innovation Team of Beijing University of Chinese Medicine(No.2011-CXTD-13)
