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水飞蓟宾、槲皮素固体分散体的热力学性质研究
Study on the Thermodynamic Properties for Solid Dispersion of Silybin and Quercetin
【作者】 韩伟;
【导师】 白同春;
【作者基本信息】 苏州大学 , 物理化学, 2009, 硕士
【摘要】 水飞蓟宾、槲皮素均为难溶性药物,溶解度和溶出速度差,提高生物利用度是研究的一个重要方面。将难溶性药物制备成固体分散体是改善其溶出速度有效方法之一。本文分别以水飞蓟宾、槲皮素与不同载体制备成固体分散体,研究其热力学性质和相关光谱性质。研究内容包括:1.以Poloxamer 188为载体,熔融法制备水飞蓟宾+Poloxamer 188固体分散体,利用差示扫描量热法(DSC)测定固体分散体的DSC曲线,考察相变温度和相变焓随固体分散体组成的变化情况,即T-wt%和ΔfusHw-wt%关系。结合傅立叶红外光谱(IR)和X-射线粉末衍射(XRD)分析水飞蓟宾和Poloxamer 188分子间的相互作用以及样品晶型的变化。并运用Flory-Huggins理论模型对实验结果进行关联。2.以PEG 6000为载体,熔融法制备槲皮素+PEG 6000固体分散体,利用差示扫描量热法(DSC)测定固体分散体的DSC曲线,考察相变温度和相变焓随分散体组成的变化情况,即T-wt%和ΔfusHw-wt%关系。结合傅立叶红外光谱(IR)和X-射线粉末衍射(XRD)分析槲皮素和PEG 6000分子间的相互作用以及样品晶型的变化。3.以Poloxamer 188为载体,熔融法制备槲皮素+Poloxamer 188固体分散体,利用差示扫描量热法(DSC)测定固体分散体的DSC曲线,考察相变温度和相变焓随分散体组成的变化情况,即T-wt%和ΔfusHw-wt%关系。结合傅立叶红外光谱(IR)和X-射线粉末衍射(XRD)分析槲皮素和Poloxamer 188分子间的相互作用以及样品晶型的变化。4.测定胆酸钠+水飞蓟宾混合体系的比热,对比热数据进行分析。
【Abstract】 Silybin and Quercetin are mainly hydrophobic organic compounds. Solid dispersion technology can improve the dissolution rate of hydrophobic drugs. Thermodynamic properties of solid dispersions of silybin and quercetin were studied in this work. It included:1. Solid dispersions of silybin with Poloxamer188 was prepared by fusion-cooling method. In this work, the thermodynamic properties of mixture of silybin + poloxamer 188 were determined. One interest is the study on the possible effect of poloxamer 188 on reducing the melting temperature of silybin + Poloxamer188 solid dispersions. The melting temperature (Tfus) and the enthalpy of fusion,ΔfusH, were measured by differential scanning calorimetry (DSC). The phase diagram and the enthalpy diagram were constructed from experimental data. The data were fitted to the Flory–Huggins model. FT-IR spectroscopy and powder X-ray diffraction were performed to elucidate the structure and possible drug–carrier interactions.2. Solid dispersion of PEG 6000 with quercetin was prepared by fusion-cooling method. The T-wt% andΔfusHw-wt% diagrams were constructed by DSC method. The melting temperature (Tfus) and the enthalpy of fusion,ΔfusH, were measured by differential scanning calorimetry (DSC). The phase diagram and the enthalpy diagram were constructed from experimental data. FT-IR spectroscopy and powder X-ray diffraction were performed to elucidate the structure and possible drug–carrier interactions.3. Solid dispersion of quercetin with Poloxamer 188 was prepared by fusion-cooling method. The T-wt% andΔfusHw-wt% diagrams were constructed by DSC method. The melting temperature (Tfus) and the enthalpy of fusion,ΔfusH, were measured by differential scanning calorimetry (DSC). The phase diagram and the enthalpy diagram were constructed from experimental data. FT-IR spectroscopy and powder X-ray diffraction were performed to elucidate the structure and possible drug–carrier interactions.4.The heat capacity of the system of Sodium cholate + Silybin were determined by DSC.
【Key words】 silybin; quercetin; PEG 6000; Poloxamer 188; phase diagram; enthalpy of fusion; heat capacity;