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目的:制备双苯氟嗪-聚乙二醇6000分散体,计算双苯氟嗪在聚乙二醇分散过程中的热力学参数。方法:研磨法制备双苯氟嗪-固体分散体,采用红外吸收光谱、X线粉末衍射光谱、差示扫描量热分析法表征分散体的形成,考察不同研磨时间、不同载体比例对形成固体分散体的影响,应用相溶解度法测定不同温度下双苯氟嗪在聚乙二醇中的溶解度,计算热力学参数。结果:固体分散体的溶出速率明显高于原料药及物理混合物,而且载体比例越大,分散体的溶出速率越快,药/载体质量比为1∶3、研磨3 h的固体分散体10 min累计溶出为原料药的4.75倍,分散体的表观稳定常数随温度的升高而减小,25℃时分散体形成过程的ΔrH=-267.3 kJ·mol-1,ΔrS=-0.786 kJ·mol-1·K-1,ΔrG=-33.13 kJ·mol-1。结论:制备的双苯氟嗪-聚乙二醇固体分散体能加速体外溶出,药物与载体形成低共熔物,双苯氟嗪在聚乙二醇分散过程中的主要驱动力为焓驱动。
OBJECTIVE: To prepare dipfluzine-polyethylene glycol 6000 dispersion and calculate the thermodynamic parameters of dipfluzine during the dispersion of polyethylene glycol. METHODS: Dipfluzine-solid dispersions were prepared by grinding method. The formation of dispersions was characterized by infrared absorption spectroscopy, X-ray powder diffraction and differential scanning calorimetry. The effects of different milling time on the formation of solid dispersion The solubility of dipfluzine in polyethylene glycol was determined by phase solubility method and the thermodynamic parameters were calculated. Results: The dissolution rate of the solid dispersion was significantly higher than that of the bulk drug and the physical mixture. The greater the proportion of the carrier was, the faster the dissolution rate of the dispersion was. The solid / dispersion ratio was 1: 3 and the solid dispersion was ground for 3 h. The cumulative dissolution rate was 4.75 times that of the drug substance. The apparent stability constant of the dispersion decreased with the increase of temperature. ΔrH = -267.3 kJ · mol-1 and ΔrS = -0.786 kJ · mol at 25 ℃ -1 · K-1, ΔrG = -33.13 kJ · mol-1. CONCLUSION: Dipfluzine-PEG dispersion can accelerate dissolution in vitro. The drug and carrier form eutectic. The main driving force of dipfluzine in PEG dispersion is enthalpy.