苯甲酸利扎曲普坦原位凝胶鼻喷剂的制备

Preparation of in situ gel of rizatriptan benzoate nasal spray

目的:一种新型治疗偏头痛的鼻喷剂——苯甲酸利扎曲普坦(RZTB)原位凝胶鼻喷剂的制备。方法:经大鼠的鼻腔灌流试验来筛选最佳浓度的吸收促进剂;通过测定胶凝温度确定原位凝胶材料泊洛沙姆407(P407)和泊洛沙姆188(P188)的合适比例;利用胶凝温度、黏度、粒径分布、喷射角度和每喷主药含量来调整处方中各组分的比例,确定RZTB原位凝胶鼻喷剂的最优处方。结果:羧甲基壳聚糖(CMCS)具有较好的吸收促进效果,制备的RZTB原位凝胶鼻喷剂的最佳处方为:20%P407、2%P188、0.1%CMCS和0.5%RZTB。结论:本实验所得的RZTB原位凝胶鼻喷剂,制备工艺简单可行,为曲坦类药物新剂型的研发提供了依据。

OBJECTIVE To prepare a new type of in situ gel of rizatriptan benzoate(RZTB)nasal spray for the treatment of migraine.METHODS The optimal concentration of absorption enhancer was selected by nasal perfusion test in rats;the suitable ratio of in situ gel material Poloxamer 407(P407)and Poloxamer 188(P188)was determined by measuring the gelation temperature;the optimal formulation of RZTB in situ gel nasal spray was determined by adjusting the ratio of each component in the formulation through gelation temperature,viscosity,particle size distribution,spray angle,and main drug content per spray.RESULTS Carboxymethyl chitosan(CMCS)was selected to be absorption enhancer.The best formulation of RZTB in situ gel nasal spray is:20%P407,2%P188,0.1%CMCS and 0.5%RZTB.CONCLUSION The preparation process of in situ gel of RZTB nasal spray was simple and feasible,which could provide basis for the development of new formulations for the triptans.