格列美脲结晶抑制剂对其固体分散体的影响

发布时间：2018-06-07 02:14

  本文选题：格列美脲 + 过饱和溶液　； 参考：《沈阳药科大学学报》2017年06期

【摘要】：目的快速地筛选格列美脲的结晶抑制剂,比较不同结晶抑制剂对其制备的格列美脲固体分散体的影响。方法通过溶剂改变法制备格列美脲的过饱和溶液,筛选出药物具有明显沉降趋势的过饱和度。进一步考察Soluplus、VA64、HPMC-E5、PVP K30、F68、PEG6000和PEG4000等聚合物抑制格列美脲的过饱和溶液的沉降能力,选择有抑晶作用的聚合物制备格列美脲固体分散体。考察溶出较好的固体分散体在非漏槽条件,pH4.5的PBS溶液中维持药物过饱和溶液的能力,并用偏光显微镜法、差示扫描量热法、X-射线衍射法和红外光谱法考察药物在载体中的存在状态。结果格列美脲过饱和溶液在过饱和度约为68.20时,沉降趋势明显。聚合物对格列美脲的抑晶作用强弱为:SoluplusHPMC-E5PVP K30≥VA64F68PEG4000≥PEG6000,选取Soluplus、VA64、HPMC-E5和PVP K30为载体。采取溶剂法制备格列美脲固体分散体,不同载体制备的固体分散体都可在药物与聚合物的质量比为1∶4或1∶7时,在pH7.8PBS溶液中达到最大累计溶出量,且4h不沉降。固体分散体在非漏槽条件pH4.5的PBS溶液中维持药物过饱和溶液的能力同结晶抑制剂筛选的结果一致,而且只有VA64制备的固体分散体的抑晶作用和载体量成正相关。根据偏振光显微镜法、差示扫描量热、X-射线衍射和红外光谱考察结果,格列美脲在对其具有抑晶作用的载体制备的固体分散体中以无定型或分子形式存在。结论格列美脲结晶抑制剂能够在4h内维持其固体分散体溶液相对稳定的过饱和状态。药物在有抑晶作用的载体中以无定型或分子形式存在。
[Abstract]:Aim to screen the crystal inhibitors of glimepiride and compare the effects of different crystal inhibitors on the solid dispersion of glimepiride prepared by glimepiride. Methods the supersaturated solution of glimepiride was prepared by solvent change method. The inhibition ability of Soluplusus VA64 (HPMC-E5) PVP K30F68PEG6000 and PEG4000 on the sedimentation of supersaturated solution of glimepiride was investigated. The solid dispersion of glimepiride was prepared by using the suppressive polymer. The ability of dissolving solid dispersions to maintain supersaturated drug solution in PBS solution with pH 4.5 was investigated by polarizing microscope. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and infrared spectroscopy (IR) were used to investigate the existence of drugs in the carrier. Results when supersaturated solution of glimepiride was about 68.20, the settlement trend was obvious. The inhibitory effect of polymer on glimepiride was as follows: Soluplus HPMC-E5PVP K30 鈮，

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