静脉用中药注射剂成品输液物理性质考察

Experimental investigation of the physical properties of intravenous traditional Chinese medicine injections

目的考察用氯化钠注射液(NS)和5%葡萄糖注射液(5%GS)调配的29种中药注射剂成品输液的物理性质,为中药注射剂成品输液质量控制与检测方法提供参考。方法2022年7—12月按照临床常用给药剂量与药物浓度,29种静脉用中药注射剂于洁净环境下用NS或5%GS调配,考察室温(20~23℃)4 h成品输液性状、丁达尔效应、浊度、色度、不溶性微粒、pH、550 nm与420 nm吸光度[D(λ)550 nm与D(λ)420 nm]等物理参数及其变化。成品输液为澄明液体、颜色没有变化、不产生气体、不产生结晶或沉淀、不产生丁达尔效应、不溶性微粒符合《中国药典》规定;与0 h比较,浊度变化<0.5 NTU、pH变化<1.00、D(λ)550 nm变化<0.010、无色成品输液D(λ)420 nm变化<0.040,判断成品输液质量符合要求。结果29种静脉用中药注射剂分别用NS和5%GS调配成58种成品输液,其中用NS调配苦黄注射液立即产生弱丁达尔效应;用NS调配冠心宁注射液、苦黄注射液、舒肝宁注射液、舒血宁注射液、黄芪注射液、双黄连注射液、醒脑净注射液、痰热清注射液或用5%GS调配灯盏细辛注射液、肾康注射液、醒脑净注射液、痰热清注射液的成品输液,外观性状无明显变化,浊度、pH指标符合要求,但是不溶性微粒超出《中国药典》2020年版之规定或与0 h比较D(λ)550 nm≥0.010。其他46种成品输液各项指标均符合要求。结论29种中药注射剂,苦黄注射液、冠心宁注射液、舒肝宁注射液、舒血宁注射液、黄芪注射液、双黄连注射液推荐用5%GS调配;灯盏细辛注射液、肾康注射液推荐用NS调配;其他药物可以用NS或5%GS调配,但是醒脑净注射液与痰热清注射液的成品输液应在2 h内使用。溶液性状等物理参数及变化可作为静脉用中药注射剂成品输液质量控制指标,方法简单、可行。

Objective To examine the physical properties of 29 traditional Chinese medicine(TCM)injections when infused with 0.9%sodium chloride injection(NS)and 5%dextrose injection(5%GS),thus providing reference for quality control and testing methods of TCM injections.Methods From July to December 2022,the 29 intravenous TCM injections were prepared using NS or 5%GS in a clean environment according to the commonly used clinical dosage and drug concentration.The finished infusions were observed for physical characteristics,Tyndall effect,turbidity,color intensity,insoluble particles,pH,and absorbance at 550 nm and 420 nm,within 4 hours at room temperature(20-23℃).Acceptable quality of the finished infusion was defined as follows:clear liquid,no change in color,no gas,no crystallization or precipitation,no Tyndall effect,insoluble particles complying with the Chinese Pharmacopoeia,turbidity change<0.5NTU,pH change<1.00,D(λ)550 nm change<0.010,and colorless finished infusion with D(λ)420 nm change<0.040 when compared to the initial state(0 hours).Results The 29 intravenous TCM injections were prepared using both NS and 5%GS,resulting in a total of 58 finished infusions.Among them,the finished infusion of Kuhuang injection prepared with NS immediately exhibited a weak tyndall effect.The finished infusions of Guanxinning injection,Kuhuang injection,Shuganning injection,Shuxuening injection,Huangqi injection,Shuanghuanglian injection,Xingnaojing injection,Tanreqing injection prepared with NS,as well as Dengzhanxixin injection,Shenkang injection,Xingnaojing injection,Tanreqing injection prepared with 5%GS,showed no apparent changes in appearance.The turbidity and pH parameters met the requirements.However,the insoluble particles exceeded the standards speci fied in the Chinese Pharmacopoeia 2020 edition,or the D(λ)550 nm≥0.010 when compared to the initial state(0 hours).The remaining 46 finished infusions met all the specified criteria.Conclusions Among the 29 types of TCM injections,Kuhuang injection,Guanxinning injection,Shuganning injection,Shuxuening injection,Huangqi injection,and Shuanghuanglian injection are recommended to be prepared using 5%GS,and Dengzhanxixin injection and Shenkang injection are recommended to be prepared using NS.Other medications can be prepared using either NS or 5%GS.However,the finished infusions of Xingnaojing injection and Tanreqing injection should be used within 2 hours.The physical parameters and their changes,including solution appearance,can serve as quality control indicators for finished infusions of intravenous TCM injections,which is simple and feasible.