左乙拉西坦pH敏感鼻用凝胶的制备及体外质量评价  

Preparation and In Vitro Quality Evaluation of Levetiracetam pH Sensitive Nasal Gel

作　　者：李爽 谷福根[2] 丛志新 吴春芝[2] LI Shuang;GU Fu-gen;CONG Zhi-xin;WU Chun-zhi(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China;Affiliated Hospital,Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学药学院,呼和浩特010110 [2]内蒙古医科大学附属医院,呼和浩特010050

出　　处：《中国药学杂志》2021年第7期559-566,共8页Chinese Pharmaceutical Journal

摘　　要：目的制备左乙拉西坦(levetiracetam, LEV)pH敏感鼻用凝胶并对其体外质量进行评价。方法首先对LEV的最稳定pH值和药物经鼻黏膜吸收理想促渗剂进行研究,然后以卡波姆940(CP940)和羟丙甲基纤维素(HPMC)作为鼻用凝胶的基质材料,制备LEV的pH敏感鼻用凝胶,最后对该制剂pH值、黏度、药物和防腐剂的含量、体外释放度、每喷剂量等质量指标进行评价。结果药物的最稳定pH在4.5~7.0之间,药物经鼻黏膜吸收的最佳促渗剂为5%的HP-β-CD,最后确定LEV的pH敏感鼻用凝胶的理想处方组成为:5%的LEV、0.5%的CP940、0.8%的HPMC、5%的HP-β-CD,0.05%的尼泊金乙酯以及适量水。该制剂外观、pH值、黏度、药物和防腐剂的含量、体外释放度、每喷剂量等指标均符合鼻用制剂质量要求。结论所制备LEV的pH敏感鼻用凝胶组成合理,制备工艺简单,质量稳定,使用方便,是一种有望替代口服与注射给药的理想剂型。OBJECTIVE To prepare a pH-sensitive nasal gel of levetiracetam(LEV)and further investigate its in vitro quality.METHODS The most stable pH and optimal nasal absorption enhancer of LEV were firstly studied.The pH sensitive nasal gel of LEV was then prepared by using carbomer 940 and HPMC as main base excipients.Finally,the main quality items of the LEV nasal gel such as appearance,pH value,viscosity,contents of the drug and preservative,in vitro release,dose per spray were investigated.RESULTS The most stable pH range and optimal absorption enhancer of LEV were found to be between pH 4.5 to 7.0 and 5%of HP-β-CD,respectively.The ideal formulation of the above LEV nasal gel consisted of 5%LEV,0.5%CP940,0.8%HPMC,5%HP-β-CD,0.05%ethylparaben and suitable amount of purified water.Additionally,the quality items such as appearance,pH value,viscosity,contents of the drug and preservative,in vitro release,drug dose per spray of the LEV nasal gel all conformed to the relevant quality requirements of nasal preparations for human use.CONCLUSION The pH sensitive nasal gel of LEV will be an ideal alternative to the oral and parenteral preparations of the drug due to its reasonable formulation composition,simple preparation process,stable quality and convenient use.

关 键 词：左乙拉西坦 pH敏感鼻用凝胶 处方筛选 卡波姆 羟丙甲基纤维素 质量评价 

分 类 号：R944[医药卫生—药剂学]