卡马西平pH/磁双重敏感性凝胶小球的制备及性能**

摘要

背景：卡马西平药物剂型存在设计不足或缺陷，导致该药吸收不规则，个体间药代动力学差异大，治疗浓度范围窄，临床上需要进行治疗药物监测。目的：制备卡马西平pH/磁双重敏感性凝胶小球，评价其性能。方法：以壳聚糖、海藻酸钠和 Fe3O4纳米粒为主要载体材料，采用离子凝胶法成功将抗癫痫药卡马西平载入卡马西平pH/磁双重敏感性凝胶小球，并采用L9(34)正交试验设计优化凝胶小球处方组成及制备工艺，通过扫描电镜法、红外光谱法对凝胶小球的表面形态及内部结构进行表征，并检测其超顺磁性、溶胀度和体外释放性能。结果与结论：最佳制备工艺条件为：壳聚糖浓度0.5%，海藻酸钠浓度1.5%，氯化钙浓度2.0%，磁载比为1∶2。所得凝胶小球形状圆整，表面光滑，平均包封率为94.36%，载药量为25.05%，粒径为1.0-2.0 mm。卡马西平pH/磁双重敏感性凝胶小球具有超顺磁性，溶胀度与介质pH关联，在模拟胃液中2 h，累积释放率达22.77%，转移到模拟肠液中24 h后，累积释放率达91.63%。表明卡马西平pH/磁双重敏感性凝胶小球处方组成合理，制备工艺可行，具有明显的pH敏感性和磁敏感性，控释性能良好。%BACKGROUND:The faults or defects in pharmaceutical dosage form designed for carbamazepine may lead to irregular drug absorption, great individual differences between the pharmacokinetics, narrow therapeutic concentration range, and the therapeutic drug monitoring for this drug. OBJECTIVE:To prepare a magnetic/pH double sensitive hydrogel beads carrying carbamazepine and to evaluate its properties. METHODS:Using chitosan, alginate and Fe3O4 nanoparticle as carrier materials, the magnetic/pH double sensitive hydrogel beads carrying anti-epileptic carbamazepine were prepared, and the composition and preparation technology were optimized by orthogonal test of L9(34). The surface morphology and structure of the hydrogel beads were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy respectively. Also, the superparamagnetism, swel ing and release in vitro of hydrogel beads were determined. RESULTS AND CONCLUSION:The optimized preparation technology were described as:0.5%(w/v) chitosan, 1.5%(w/v) alginate, 2.0%(w/v) calcium chloride, and 1:2 ratio for magnetic versus carrier materials. The hydrogel beads under the optimal preparation conditions showed a round shape and smooth surface, and average encapsulation efficiency, loading efficiency and hydrogel beads diameter were 94.36%, 25.05%and 1-2 mm respectively. The hydrogel beads appeared to have superparamagnetism, the swel ing degrees were associated with pH value of medium, and the sequential release amount of carbamazepine from the hydrogel beads in simulated gastric fluid was 22.77%for 2 hours. Then, the beads were moved to the simulated intestinal fluid, and this value approached 91.63%for 24 hours. Experimental findings indicate that, the composition and preparation technology of magnetic/pH double sensitive hydrogel beads carrying carbamazepine was rational and feasible, and hydrogel beads show obvious pH sensitivity and magnetic sensitivety. The control ed-release effect of hydrogel beads in vitro is also good.