| 摘要: |
| 【目的】制备氟苯尼考（FF）联合载体固体分散体（FF/SDs），并对其特性进行表征。【方法】采用溶剂蒸发法制备FF/SDs，通过单因素试验考察载体种类（泊洛沙姆188(F68)、尿素、PEG4000、PEG6000、聚维酮k30（PVPk30））、溶剂种类（甲醇、乙醇、丙酮）、旋转蒸发温度（50，60，70，80和90 ℃）和超声时间（5，10，15和20 min）及转速(70,90,110,130,150 r/min)等对FF饱和溶解度的影响。在单因素试验的基础上，选取联合载体材料种类、联合载体质量比、溶剂、旋转蒸发温度等4个因素，设计L9（34）正交试验，确定制备FF/SDs的最佳条件。采用差示扫描量热法和X射线粉末衍射法对最佳条件下制备的FF/SDs进行验证，并测定其累计溶出度。【结果】以尿素、PVPk30为联合载体，FF、PVPk30、尿素质量比为1∶4∶5，甲醇为溶剂，旋转蒸发温度为80 ℃，最佳转速为150 r/min,360 W超声波处理10 min，可得到最优FF/SDs。FF、FF/SDs和二者物理混合物（PM）的差示扫描量热（DSC）图谱、X射线衍射图谱和溶出度存在明显差异，FF原粉是晶体态的片层结构，FF/SDs则为无定形态。最佳条件下制备的FF/SDs饱和溶解度为3.11 mg/mL，是FF原药和PM的2.43和2.07倍。6 min时FF/SDs累计溶出度达94.35%，是同一时间FF原药的3.72倍。【结论】得到了制备FF/SDs的最佳条件，且联合载体尿素/PVPk30（m（尿素）∶m（PVPk30）=5∶4）较单一载体能更好地提高氟苯尼考的水溶性，并加快其溶出。 |
| 关键词: 氟苯尼考 固体分散体 联合载体 聚维酮k30 尿素 |
| DOI： |
| 分类号: |
| 基金项目:四川农业大学学科建设双支计划项目（03571158） |
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| Increasing florfenicol solubility by combined urea and PVPk30 |
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LIU Chang,ZHOU Junjie,FU Hualin,et al
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| Abstract: |
| 【Objective】The solid dispersions containing florfenicol and combined carriers were prepared by solvent evaporation method and characterized.【Method】The influencing factors including carrier type (F68,urea,PEG4000,PEG6000 and PVPk30),solvent (methanol,ethanol and acetone),rotary evaporation temperature (50,60,70,80 and 90 ℃),ultrasonic time (5,10,15 and 20 min) and rotational speed (70,90,110,130,150 r/min)were investigated using saturated solubility of florfenicol as indicator.On the basis of single factor experiments,the factors were selected and L9(34) orthogonal test was designed to determine the best conditions for FF/SDs preparation.Then X-ray powder diffraction and differential scanning calorimetry methods were used to validate FF/SDs,and measure its cumulative dissolution.【Result】It showed that the combined use of urea and povidone,the mass ratio of florfenicol,PVPk30 and urea was 1∶4∶5,methanol as solvent,rotary evaporation temperature is 80 ℃,rotational speed is 150 r/min and 360 W ultrasonic processing 10 min had the optimal formula.There were significant differences in X-ray,DSC diagrams and dissolution rate of FF, FF/SDs and PM.The structure of FF was crystal lamellar,while that of SDs was amorphous.The saturated solubility of FF/SDs was 3.11 mg/mL at 37 ℃,which was 2.43 folds of florfenicol and 2.07-folds of physical mixtures.The cumulative solubility was 94.35%,which was 3.72 folds of florfenical.【Conclusion】The solubility of florfenicol solid dispersion with combined carrier urea/PVPk30（m(urea）∶m(PVPk30)=5∶4) was much better than single carrier,and the dissolution was increased significantly. |
| Key words: florfenicol (FF) solid dispersion combined carrier PVPk30 urea |
