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.
XU Ming-zhe, LIU Yi, HE Lan, ZHAO Xia, SUN Hui-min, ZHANG Xia, GUAN Xiao-dong, SHI Lu-wen
. Study of key factors influencing the quality of bromhexine hydrochloride injectable preparations in clinical use[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(2)
: 359
-369
.
DOI: 10.16155/j.0254-1793.2021.02.20
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