地塞米松磷酸钠温度敏感原位凝胶的体外释药特性

Release in vitro of dexamethasone sodium phosphate from thermosensitive in situ gels

目的考察地塞米松磷酸钠温度敏感原位凝胶的体外释药特性。方法采用旋转流变仪测定黏度随温度的变化;无膜溶出法测定地塞米松磷酸钠温度敏感原位凝胶的溶蚀行为,以pH7.2的磷酸盐缓冲溶液为释放介质,温度(37±0.5)℃,水平振荡(频率50r/min,振幅2.5cm);采用高效液相色谱法(high performance liquid chromatography,HPLC)测定凝胶的释药行为,色谱柱:DiamonsilTM C18(250mm×4.6mm,5μm),流动相:三乙胺水溶液-甲醇-乙腈(38∶28∶34),流速1.0ml/min,紫外检测波长242nm。结果当温度接近相转变温度时,黏度陡然上升。以2mlpH7.2的磷酸盐缓冲溶液为释放介质,体外凝胶的溶蚀和药物的释放均遵循零级动力学方程,其累积溶蚀百分量(Q1)和累积释放百分量(Q2)对时间t的回归方程分别为Q1=0.8238t(r=0.999,P<0.01)和Q2=0.8431t(r=0.999,P<0.01),且2者线性相关,Q2=1.0232Q1(r=0.998,P<0.01)。结论采用无膜溶出法测定地塞米松磷酸钠温度敏感型原位凝胶的累积溶蚀百分量与其累积释放百分量相等,体外的溶蚀行为与释放行为遵循零级动力学方程,二者间存在良好的线性关系。

Objective To investigate the release feature of dexamethasone sodium phosphate from thermosensitive in situ gels in vitro. Methods Rotation rheometer was used to measure the changes of viscosity with temperature. The membraneless model was applied in assessing corrosion behavior of gel using a thermostatic shaker （50 r/min） at an amplitude of 2.5 cm, taking phosphate buffered solution （pH 7.2） as releasing media. The release behavior was investigated by HPLC on a Cls reverse column DiamonsilTM （ 250mm×4.6mm,5μm）. The mobile phase consisted of triethylamine solution-methanol-acetonitrile （38： 28： 34）, pumped at 1.0 ml/min, and the detection wavelength was set at 242 nm. Results When the temperature was near to the sol-gel transition temperature, the viscosity rose suddenly. Taking dexamethasone sodium phosphate （2 ml, pH 7.2） as media, the gel dissolution and drug release rate followed the zero order kinetics, and the cumulative gel dissolution （Q1） and cumulative drug release （ Q2 ） equations were Q1 = 0. 8238t （r = 0. 999, P 〈0.01 ） and Q2 =0. 8431t （r =0. 999, P 〈0.01 ） , respectively. There was good liner relationship between cumulative drug release and drug release time. Conclusion The drug release behavior of thermosensitive in situ gels is clearly shown in our experiment.