螺旋霉素超细粉的喷干法和反溶剂法制备及性质研究

Preparation and properties of spiramycin micro-powder by spray drying and antisolvent method

目的螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可以很好地解决这些问题;方法采用了两种代表性的方法制备螺旋霉素的超细粉:分别为喷雾干燥法和反溶剂法;并以粒径为指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果两种方法的最佳条件为:喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均粒径为(1638±10.99)nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪(DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论与喷雾干燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于制药业,为微粉技术提供技术思路。

Objective Spiramycin powder has large particle size and serious agglomeration,which greatly restricts its clinical application.It has been reported that ultrafine powder preparation technology can solve these problems well.Methods Two representative methods were used to prepare spiramycin ultrafine powder:spray drying method and anti-solvent method.Aim for particle size,single factor experimental optimization was used to obtain the best results.The particle size,morphology and physical and chemical properties of the powders prepared by the above two methods were compared respectively.Results The optimal conditions of the two methods were as follows:the feeding speed of spray drying was 5 mL/min,the atomized air speed was 800 L/h,the inlet temperature was 150℃,the outlet temperature was 85℃,and the average particle size was 1638±10.99 nm.The anti-solvent method was tested at 25℃,and the ratio of solvent to anti-solvent was 1:5.The optimal stirring speed was 1000 r/min,and the average particle size was 230±7.31 nm.The above results were characterized by scanning electron microscopy(SEM),dynamic light scattering(DLS),fourier transform infrared spectroscopy(FTIR),differential scanning calorimeter(DSC)and X-ray diffraction(XRD).By gas chromatography,the solvent residues in both methods met the ICH minimum standard(5000 ppm).Conclusion Compared with spray drying method,spiramycin prepared by anti-solvent method has smaller particle size,better powder dispersion and higher solubility.Therefore,spirase micropowder prepared by anti-solvent method is more suitable for pharmaceutical industry and provides technical ideas for micropowder technology.