帕瑞昔布钠鼻用温敏凝胶的制备及其体外性质研究  

Preparation of parecoxib sodium thermosensitive nasal gel and its in vitro properties

作　　者：黄晶 谷福根[1] 吴春芝[1] HUANG Jing;GU Fu-gen;WU Chun-zhi(Affiliated Hospital,Inner Mongolia Medical University,Hohhot 010050;The First Hospital of Hohhot City,Hohhot 010030)

机构地区：[1]内蒙古医科大学附属医院,呼和浩特010050 [2]呼和浩特市第一医院,呼和浩特010030

出　　处：《中南药学》2023年第8期2046-2052,共7页Central South Pharmacy

摘　　要：目的 制备帕瑞昔布钠鼻用温敏凝胶(PS-TNG)并对其体外性质进行评价。方法 以胶凝温度为主要观察指标,采用星点设计-效应面法对PS-TNG处方进行优化,然后以离体羊鼻黏膜为模型,采用Franz透皮扩散池法筛选PS最佳促渗剂,最后制备PS-TNG并对其体外性质进行研究。分别测定该制剂的胶凝温度、胶凝时间、pH值、体外溶蚀率、药物释放率以及药物释放度,并考察温度和转速对制剂黏度的影响以及制剂的膨胀系数和持水能力。结果 PS-TNG理想处方组成为:5.0%PS、20.88%F127、3.28%F68、0.28%HPMC、5.0%HP-β-CD、0.05%尼泊金乙酯及适量水。测得PS-TNG的胶凝温度为32.2℃,胶凝时间为48.2 s,pH值为7.4;PS-TNG体外累积溶蚀与药物累积释放量间具有良好的线性关系(r=0.9997);制剂释放度试验表明,PS-TNG具明显缓释特征。此外,发现温度和搅拌对制剂的黏度均有明显影响,该制剂的持水能力强且膨胀系数小。结论 PS-TNG处方组成合理,制备工艺简单,其胶凝温度、胶凝时间、p H值、膨胀系数和持水能力适宜,药物缓释作用明显,预计有良好的临床应用前景。Objective To prepare parecoxib sodium thermosensitive nasal gel(PS-TNG)and evaluate its in vitro properties.Methods The gelation temperature was used as the main evaluating index,and the formulation of PS-TNG was optimized by central composite design-response surface method.Meanwhile,the ideal nasal absorption enhancer for PS and its concentration were selected by the Franz diffusion cell method with the in vitro sheep nasal mucosa as the test model.Finally,PS-TNG was prepared and its main in vitro properties were determined.The gelation temperature,gelation time,pH,in vitro erosion and release of the drug thermo-sensitive nasal gel were investigated.The effect of temperature and stirring speed on the viscosity of PS-TNG,expansion coefficient and waterholding capacity was also investigated.Results The optimized formulation of PS-TNG consisted of 5.0%PS,20.88%F127,3.28%F68,0.28%HPMC,5.0%HP-β-CD,0.05%ethylparaben and appropriate amount of purified water.The gelation temperature,gelation time and pH of PS-TNG were 32.2℃,48.2 s and 7.4,respectively.There was a good linearity between the in vitro cumulative erosion of PS-TNG and its cumulative drug release(r=0.9997).Additionally,the cumulative release of PS from the nasal gel showed obvious sustained release behavior.The temperature and stirring speed had obvious effect on the viscosity of the nasal gel.Meanwhile,PS-TNG showed low expansion coefficient and good water-holding capacity.Conclusion PS-TNG has good clinical application prospects due to its reasonable formulation composition,easy preparation,appropriate gelation temperature,gelation time,low expansion coefficient,good water-holding capacity and obvious in vitro sustained drug release characteristics.

关 键 词：帕瑞昔布钠 鼻用温敏凝胶 星点设计-效应面法 吸收促渗剂 体外性质 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]