复方土槿皮酊与外用液体药用高密度聚乙烯瓶相容性研究

Compatibility Between Compound Tujinpi Tincture and High-Density Polyethylene Bottle

目的 探讨复方土槿皮酊与外用液体药用高密度聚乙烯瓶的相容性。方法 采用高效液相色谱法测定苯甲酸和水杨酸的含量,按2020年版《中国药典(四部)》通则0711第一法(毛细管柱法)测定乙醇体积分数。依据《药品包装材料与药物相容性试验指导原则》,通过加速试验[温度(40±2)℃、相对湿度(90±10)%条件下放置6个月],长期试验[温度(25±2)℃、相对湿度(60±10)%条件下放置12个月],加严条件的影响因素试验条件下[温度(25±2)℃、相对湿度(20±5)%(低湿)和温度(25±2)℃、相对湿度(90±10)%(高湿)条件下分别放置6个月],以及多次开启试验,考察高密度聚乙烯瓶包装的复方土槿皮酊实际使用过程中苯甲酸、水杨酸含量及乙醇体积分数的变化。结果 苯甲酸和水杨酸的进样量分别在0.102~1.812μg和0.050~0.906μg范围内与峰面积线性关系良好(R~2=0.999 9,n=5);精密度、稳定性、重复性试验结果的RSD均小于0.5%(n=6);平均加样回收率分别为99.34%和99.24%,RSD分别为0.72%和0.92%(n=6)。加速试验、长期试验及加严条件的影响因素试验(低湿和高湿)条件下,3批样品均为黄棕色至红棕色的澄清溶液,无沉淀、浑浊、变色,无微粒、块状物析出。在加速试验中,3批样品中苯甲酸和水杨酸平均含量及乙醇平均体积分数分别为120.95~121.27 mg/mL、60.30~61.45 mg/mL、78.49%~79.49%,RSD均小于2.0%(n=18);在长期试验中,分别为121.06~121.89 mg/mL、60.49~61.81 mg/mL、79.40%~79.70%,RSD均小于2.0%(n=18);在低湿加严条件的影响因素试验中,分别为121.64~122.89 mg/mL、60.55~61.88 mg/mL、79.23%~80.05%,RSD均小于2.0%(n=18);在高湿加严条件的影响因素试验中,分别为121.11~122.99 mg/mL、60.51~61.88 mg/mL、79.45%~80.41%,RSD均小于2.0%(n=18)。多次开启试验结果显示,3批样品中苯甲酸和水杨酸平均含量及乙醇平均体积分数分别为121.86~123.90 mg/mL、60.60~62.08 mg/mL、79.74%~80.57%,RSD均小于2.0%(n=9)。结论 所建立的高效液相色谱法结果准确、精密度和重复性均良好,可用于复方土槿皮酊中苯甲酸和水杨酸的含量测定。外用液体药用高密度聚乙烯瓶与复方土槿皮酊的相容性良好,可保证复方土槿皮酊的质量稳定。

Objective To investigate the compatibility between Compound Tujinpi Tincture and high-density polyethylene(HDPE)bottle for topical liquid medicine.Methods The content of benzoic acid and salicylic acid was determined by the high-performance liquid chromatography(HPLC)method,and the volume fraction of ethanol was determined by the capillary column method according to the general rule 0711 of the Chinese Pharmacopoeia(2020 Edition,VolumeⅣ).According to the Guidelines of Evaluating Compatibility Between Pharmaceutical Packaging and Pharmaceuticals,the accelerated test[placed at a temperature of(40±2)℃and a relative humidity of(90±10)%for 6 months],long-term test[placed at a temperature of(25±2)℃and a relative humidity of(60±10)%for 12 months],special requirements test[placed at a temperature of(25±2)℃and a relative humidity of(20±5)%for 6 months(low humidity);placed at a temperature of(25±2)℃and a relative humidity of(90±10)%for 6 months(high humidity)],and multiple open test were conducted to investigate the changes in the content of benzoic acid,salicylic acid,and the volume fraction of ethanol during the actual use of Compound Tujinpi Tincture packaged with HDPE bottles.Results The linear ranges of benzoic acid and salicylic acid were 0.102-1.812μg and 0.050-0.906μg(R2=0.9999,n=5),respectively,the RSDs of precision,stability,and repeatability test results were all lower than 0.5%(n=6),and the average recoveries of benzoic acid and salicylic acid were 99.34%and 99.24%,with RSDs of 0.72%and 0.92%(n=6),respectively.Under the conditions of accelerated test,long-term test,and special requirements test(low humidity and high humidity),all three batches of samples were clear solutions ranging from yellow-brown to reddish-brown,with no precipitation,turbidity,or discoloration,and no precipitation of particles or blocky substances.In the three batches of samples,average content of benzoic acid and salicylic acid,and the average volume fraction of ethanol in the accelerated test were 120.95-121.27 mg/mL,60.30-61.45 mg/mL,and 78.49%-79.49%,with RSDs<2.0%(n=18),those in the long-term test were 121.06-121.89 mg/mL,60.49-61.81 mg/mL,and 79.40%-79.70%,with RSDs<2.0%(n=18),those in the special requirements test(low humidity)were 121.64-121.89 mg/mL,60.55-61.88 mg/mL,and 79.23%-80.05%,with RSDs<2.0%(n=18),those in the special requirements test(high humidity)were 121.11-122.99 mg/mL,60.51-61.88 mg/mL,and 79.45%-80.41%,with RSDs<2.0%(n=18).The results of the multiple open test showed that the average content of benzoic acid and salicylic acid,and the average volume fraction of ethanol in samples were 121.86-123.90 mg/mL,60.60-62.08 mg/mL,and 79.74%-80.57%,with RSDs<2.0%(n=9).Conclusion The established HPLC method has accurate results,good precision and repeatability,which can be used for the determination of benzoic acid and salicylic acid in Compound Tujinpi Tincture.The compatibility between external liquid medicinal HDPE bottles and Compound Tujinpi Tincture is good,and the packaging can ensure the stable quality of Compound Tujinpi Tincture.