磷酸泰乐菌素脂质体的制备及体外释放动力学研究

Preparation and in vitro Release of Phosphate Tylosin Liposome

关键词:  磷酸泰乐菌素  脂质体  硫酸铵梯度法  正交设计  体外释放

Key words:  phosphate tylosin  liposome  ammonium sulfate gradient method  orthogonal experiment design  in vitro release

摘要:

为延长磷酸泰乐菌素在体内的作用时间，通过比较采用硫酸铵梯度法制备其脂质体制剂。以包封率为指标，分别考察磷脂与胆固醇之比、药脂比、硫酸铵浓度、孵化温度和孵化时间对包封率的影响，并在此基础上进行正交试验筛选最优处方。同时，对所得脂质体的形态、粒径及分布、包封率及体外释放动力学进行研究。结果显示，正交试验优化得到的最佳处方工艺为：磷脂与胆固醇质量比为4:l，药脂比为l:10，硫酸铵浓度为300 mmol/L，体系pH值为7.0，孵化温度为50 ?C，孵化时间为20 min。电镜下观察脂质体呈球形或类球形，分布均匀，平均粒径为6.526 um，且大部分在1 um-12 um之间，包封率为58.32%，体外释药符合Weibull方程(r=0.9764)。研究证实硫酸铵梯度法制备磷酸泰乐菌素脂质体方法可行，包封率高，稳定性好，体外释药具有一定的缓释效应。

Abstract:

To prolong the duration time, phosphate tylosin was encapsulated into liposome by means of ammonium sulfate gradient method. Entrapment efficiency was taken as a parameter and factors such as soybean phosphatidyl choline(SPC)-cholesterol(CH) ratio, drug-SPC ratio, concentration of ammonium sulfate, incubation temperature and incubation time were investigated respectively. Then the optimum preparation technology and prescription were obtained using orthogonal experiment design. The morphology, particle size and distribution, entrapment efficiency and in vitro release behavior of resulting liposome were studied synchronously. The best prescription was as follows: SPC-CH ratio was 4:1, drug-SPC ratio was 1:10, concentration of ammonium sulfate was 300 mmol/L, pH was adjusted to 7.0, incubation temperature and time were 50 ?C and 20 min apart. The received phosphate tylosin liposome was spherical or ellipsoidal in shape and uniform in size. The mean particle size was 6.526 um, with a large number of particles ranging from 1 um to 12 um. The mean entrapment efficiency was 58.32%. The process of drug release was in accordance with Weibull equation (r=0.9764). Results indicate that ammonium sulfate gradient method can be used to prepare phosphate tylosin liposome, as a result of an higher entrapment efficiency, better stability and finer sustained-release property in vitro.