头孢泊肟酯干混悬剂的制备与溶出度测定

Preparation and Dissolution Determination of Cefpodoxime Proxetil for Suspension

目的制备头孢泊肟酯干混悬剂并建立其溶出度测定方法。方法以沉降体积比、溶出度及吸湿增重等为主要评价指标确定最终处方;以pH值3.0甘氨酸-氯化钠-盐酸为溶出介质,采用紫外-可见分光光度法测定,检测波长259 nm。溶出条件:溶出温度37℃,浆法75 r·min^-1,溶出度取样时间30 min,同时考察其在溶出介质(pH值1.2盐酸、pH值4.0醋酸盐缓冲液、pH值6.8磷酸盐缓冲液、水、pH值3.0甘氨酸-氯化钠-盐酸)下的溶出曲线,取样时间为5,10,15,20,30 min。结果最终处方为头孢泊肟酯5.0%,蔗糖45.0%,交联羧甲基纤维素钠3.0%,黄原胶1.0%,羟丙甲纤维素3.72%,甘露醇35.0%,二氧化硅2.0%,阿斯巴甜1.8%,氯化钠0.8%,谷氨酸钠1.0%,黄氧化铁0.12%,甜橙味粉末香精0.05%。头孢泊肟浓度在1.66~16.6μg·mL^-1范围内呈良好的线性关系,供试品溶液在4 h内稳定。结论头孢泊肟酯干混悬剂制备工艺简单;溶出曲线测定方法操作简单,结果准确。

Objective To prepare cefpodoxime proxetil for suspension and to establish a method to determine the dissolution of it.Methods The indices,such as sedimentation volume,dissolution rate and hygroscopic weight,were used to evaluate and optimized the formation.Dissolution testing was performed using paddle method in the dissolution medium of glycine-sodium chloride-hydrochloric acid solution(pH 3.0)under stirring rate of 75 r·min^-1.The dissolution samples were obtained at 30 min and the concentration was analyzed by ultraviolet spectrophotometric method under the detection wavelength of 259 nm.The Slurry medium was used as dissolution medium,which was prepared as followed:hydrochloric acid solution(pH 1.2),water,glycine-sodium chloride-hydrochloric acid solution(pH 3.0)acetate buffer(pH 4.0),phosphate buffer(pH 6.8).The dissolution sampling time was set as 5,10,15,20 and 30 min.Results The optimal formulation was as followed:cefpodoxime proxetil 5.0%,sugar 45.0%,croscarmellose sodium 3.0%,xanthan gum 1.0%,hypromellose 3.72%,mannitol 35.0%,silicon dioxide 2.0%,aspartame 1.8%,NaCl 0.8%,sodium glutamate 1.0%,yellow ferric oxide 0.12%,and sweet orange powder essence 0.05%.Good linear correlation was achieved in the concentration range from 1.66 to 16.6μg·mL^-1.The test solution was stable after 4 h storage at room temperature.Conclusion The preparation of cefpodoxime proxetil for suspension is simple.The method is accurate and suitable for the measurements of dissolution profiles of cefpodoxime proxetil for suspensions.