根皮素-4,4-联吡啶共晶的制备表征与溶解性能测定

Preparation,Characterization and Solubility Determination of Phloretin-4,4'-Bipyridine Cocrystal

目的制备和表征根皮素-4,4'-联吡啶共晶,测定其溶解性能。方法采用液体辅助研磨法、浆式结晶法及蒸发结晶法制备根皮素-4,4'-联吡啶共晶,通过粉末X-射线衍射、热分析法、傅里叶变换红外光谱法、元素分析法对共晶进行表征分析,并对共晶样品的粉末溶出速率、平衡溶解度以及稳定性进行测定。结果用液体辅助研磨法、浆式结晶法以及蒸发结晶法制备得到高纯度根皮素-4,4'-联吡啶共晶,共晶分子物质的量之比为1:1。测得共晶在3种溶出介质中溶出行为较根皮素原料及物理混合物均具有一定优势,其中共晶在pH值1.2盐酸中平衡溶解度为活性药物成分的1.60倍,且共晶产物在高温、高湿条件下均保持稳定。结论根皮素-4,4'-联吡啶共晶稳定性良好,且表现出较好的溶解性能。

Objective To prepare and analyze phloretin-4,4'-bipyridine cocrystal,and to detect the solubility of the cocrystal.Methods A new cocrystal of phloretin with 4,4'-bipyridine(BPY)was prepared through liquid-assisted grinding,slurry crystallization,and evaporative crystallization.The cocrystal was characterized by powder X-ray diffraction,thermogravimetric analysis-differential scanning calorimetry,Fourier transform infrared spectrometer,and elemental analysis.The dissolution rate,equilibrium solubility,and stability of cocrystal samples were analyzed.Results The phloretin-4,4'-bipyridine cocrystal with higher purity was prepared in liquid-assisted grinding,slurry crystallization,and evaporative crystallization.The ratio of the amount of molecular substance was 1:1.The dissolution behavior of the cocrystal in three kinds of dissolution media reveal certain advantages compared with phloretin and the physical mixture.The solubility in pH=1.2 hydrochloric acid buffer solution was increased approximately by 1.60 folds compared to raw material.Furthermore,the cocrystal products remain stable under high temperatures and high humidity conditions.Conclusion Phloretin-4,4'-bipyridine cocrystal with good stability can significantly improve the solubility of phloretin.