双苯氟嗪-聚乙二醇固体分散体的制备及热力学

Preparation and thermodynamics of dipfluzine solid dispersion with PEG6000

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 solid dispersion （SD） of dipfluzine（DF） with PEG 6000 and investigate the thermody- namics of SD in aqueous solution. METHODS Dipfluzine SDs were prepared by solid co-grinding method under a solvent-free condition. The properties of SDs and physical mixtures were characterized by Fourier-transform infrared （FTIR）, X-ray diffrac-tion （XRD）, and differential scanning calorimetry （DSC）. The effects of grinding time and DF/PEG ratios on physiochemical properties of SDs were investigated. The solubility of DF in PEG was determined by phase solubility techniques at different tem- peramres; the values were used to calculate the thermodynamic parameters. RESULTS The dissolution rate was higher than that of dipfluzine and its physical mixture, and dissolution rate increased with the concentration of carriers. The cumulative dis solution rate at 10 min of the SD with a 1：3 DF/carrier ratio increased 4. 75 fold. The apparent stability constants of formation o{ SD decreased with the increasing of temperature. Thermodynamic parameters at 25 ℃ were as follows：△ rH = - 267.3 kJ · mol^-1, △rS = -0. 786 kJ·mol^-1.·K^-1 ,△rG = -33.13 kJ· mol^-1. CONCLUSION The solid dispersion of dipfluzine increased the dissolution rate in vitro. Eutectic compounds were produced between the dipfluzine and PEG matrix during the co-grinding process. Thermodynamic studies indicated that enthalpy is the drive force when dipfluzine disperses into the matrix of PEG.