尼可地尔鼻用温敏凝胶的处方优化及质量评价  

Formulation Optimization and Quality Evaluation of Nicorandil Thermosensitive Nasal Gel

作　　者：杨蕾 王猜 吴春芝[2] 谷福根[2] YANG Lei;WANG Cai;WU Chunzhi;GU Fugen(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》2024年第12期1142-1150,共9页Chinese Pharmaceutical Journal

摘　　要：目的优化尼可地尔(nicorandil,NIC)鼻用温敏凝胶剂(NIC-TNG)处方并对其质量进行评价。方法首先采用星点设计-效应面法,以胶凝温度和胶凝时间为考察指标,对NIC-TNG空白处方的组成进行优化;然后以离体羊鼻黏膜为实验模型,采用Franz透皮扩散池法筛选药物的最佳促渗剂;其次,考察pH值对药物溶液化学稳定性影响并确定NIC-TNG的适宜pH值;最后制备NIC-TNG并对其胶凝温度、胶凝时间、pH值、药物和防腐剂含量、体外溶蚀率与药物释放率及药物释放度等质量指标进行评价。另外,考察温度对制剂黏度的影响及制剂的膨胀系数和持水能力。结果NIC-TNG理想处方组成为:25 mg·mL^(-1)NIC、172.1 mg·mL^(-1)F127、5.0 mg·mL^(-1)F68、3.8 mg·mL^(-1)HPMC、5.0 mg·mL^(-1)三氯叔丁醇及适量水。分别测得NIC-TNG的胶凝温度为30.92℃,胶凝时间为40.82 s,pH值为6.42;药物及防腐剂含量分别为标示量的99.18%和98.72%;制剂体外溶蚀率和药物释放率均与时间呈良好线性关系(r≥0.9996);制剂释放度试验表明,NIC-TNG具明显缓释特征。此外,发现温度对制剂的黏度有明显影响,该制剂的持水能力强且膨胀系数小。结论NIC-TNG优选处方组成合理,制备工艺简单,质量稳定可控,给药方便,且具有明显缓释效果,预期有良好的临床应用前景。OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel(NIC-TNG)and further evaluate its quality.METHODS With gelling temperature and gelling time as observation indexes,the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method.Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model.The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG.Lastly,NIC-TNG was prepared and its main quality items such as the gelation temperature and time,pH,labeled contents of the drug and preservative,cumulative erosion rate,cumulative drug release,and in vitro drug release were studied,respectively.Meanwhile,the effect of temperature on the viscosity,expansion coefficient and water holding capacity of NIC-TNG were investigated.RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^(-1)NIC,172.1 mg·mL^(-1)F127,5.0 mg·mL^(-1)F68,3.8 mg·mL^(-1)HPMC,5.0 mg·mL^(-1)chlorobutanol and suitable amount of purified water.The gelation temperature and time,pH,labeled content of NIC and preservative were found to be 30.92℃,40.82 s,6.42,99.18%and 98.72%,respectively.There was a good linear correlation between the in vitro cumulative erosion rate,cumulative drug release of NIC-TNG and time(r≥0.9996).Furthermore,the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics.Temperature exhibited obvious effect on the viscosity of the nasal gel.Finally,NIC-TNG showed low expansion coefficient and good water-holding capacity.CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition,simple preparation process,stable and controllable quality,convenient use and obvious sustained drug release behavior.

关 键 词：尼可地尔 鼻用温敏凝胶 星点设计-效应面法 处方优化 吸收促渗剂 质量评价 

分 类 号：R944[医药卫生—药剂学]