摘要
目的:考察影响盐酸溴己新注射剂临床使用质量的因素。方法:通过对盐酸溴己新注射剂临床使用监测数据与国家药品质量监督抽验数据的联合分析,采用析因实验设计,考察不同pH条件下盐酸溴己新的溶解度变化,模拟临床使用条件,考察临床常用的配伍药品对盐酸溴己新注射剂稳定性的影响;同时考察了在不同滴注速度下,临床常用的4种材质的输液器对盐酸溴己新的吸附性。结果:盐酸溴己新在溶液中的溶解度与pH有关,在与偏碱性的药物(pH大于6.0)配伍使用时会出现溶解度降低导致主成分饱和析出而药液变混浊的异常现象;在常用聚氨酯类热塑性弹性体输液器(TPU)和聚氯乙烯输液器(PVC)对该药有较强的吸附作用(吸附量分别为35.4%和23.6%),聚丙烯弹性体输液器(TPE)对该药有中等吸附作用(吸附量为14.3%),吸附量与不同企业的配方组成有关(吸附量6.6%~17.8%),而低密度聚乙烯输液器(PE)对该药吸附作用则较弱(吸附量为4.3%)。而且滴注过程中滴速的快慢严重影响输液器对盐酸溴己新吸附作用:滴速越慢,吸附量越大。结论:注射剂临床配伍是导致盐酸溴己新药液浑浊质量下降的主要原因;盐酸溴己新与特定输液器材质的相容性能够影响盐酸溴己新注射剂药品质量。
Objective:To investigate to key factors which influence the quality of bromhexine hydrochloride injectable preparations during the clinical use.Methods:A case study was conducted using factorial experimental design to examine the solubility profile of bromhexine hydrochloride in various pH conditions based on the available data from post market quality surveillance and clinical monitoring.The stability of bromhexine hydrochloride combining with other medicines which were frequently used in clinical was investigated by simulating routine clinical procedure.At the same time,the compatibility between bromhexine hydrochloride with major four types of infusion apparatus was investigated at different infusion rates.Results:Bromhexine hydrochloride solubility depended on pH and the mixed solutions were getting turbid when bromhexine hydrochloride injectionable preparations were combined with other alkaline medicines with pH higher than 6.0 in clinical.Infusion apparatus which were made with thermoplastic polyurethane(TPU)and polyvinylchloride(PVC)had strong absorption effect on bromhexine and the absorption rates were 35.4%and 23.6%respectively,while thermoplastic elastomer(TPE)had modest absorption effect and the absorption rates varied between 6.6%to 17.8%with different formulations.Polyethylene(PE)had the lowest absorption rate for bromhexine hydrochloride which was 4.3%.Infusion speed was another factor which played a role on the absorption.Increased infusion speed caused higher absorption rate.Conclusion:Combining use of injection preparations in clinical is a significant factor for forming turbid solution and impaired quality,and the poor combability between infusion apparatus and injectable medicines is another contributing factor to affect medicine quality.
作者
许明哲
刘毅
何兰
赵霞
孙会敏
张夏
管晓东
史录文
XU Ming-zhe;LIU Yi;HE Lan;ZHAO Xia;SUN Hui-min;ZHANG Xia;GUAN Xiao-dong;SHI Lu-wen(Naitonal Institutes for Food and Drug Control,Beijing 102629,China;Department of Pharmacy Administration and Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China;International Research Center for Medicinal Administration,Peking University,Beijing 100191,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2021年第2期359-369,共11页
Chinese Journal of Pharmaceutical Analysis
关键词
盐酸溴己新注射液
质量影响因素
药物配伍
溶解度
相容性
bromhexine hydrochloride injections
quality influencing factors
medicine combining
solubility
compatibility
