上市利巴韦林滴眼液抑菌效力评价及分析研究

Evaluation and analysis of antimicrobial effectiveness in ribavirin eye drops

目的 评价利巴韦林滴眼液抑菌效力能否满足《中国药典》2020年版四部通则<1121>的有关要求,分析抑菌剂种类和浓度差异,探索处方优化条件。方法 按“《中国药典》四部通则1121抑菌效力检查法”对利巴韦林滴眼液制剂、不含抑菌剂的利巴韦林溶液、抑菌剂溶液(苯扎溴铵、羟苯乙酯、硫柳汞钠)进行抑菌效力考察。结果 利巴韦林溶液对细菌有一定抑菌作用,对真菌抑菌效力较低,需要添加适宜的抑菌剂以保证其抑菌效力满足要求。苯扎溴铵溶液(0.1 mg/mL)抑菌效力可达到A级标准,硫柳汞钠溶液(0.006 mg/mL)可达到B级标准,羟苯乙酯溶液(0.25 mg/mL)不满足B级标准。抽检的11份利巴韦林滴眼液制剂中,含苯扎溴铵的5份样品抑菌效力可达到A级,含硫柳汞钠的1份样品含可达到B级,羟苯乙酯的5份样品不满足抑菌效力标准要求。结论 综合抑菌效力试验数据及3种抑菌剂毒性、国内外常用浓度、限值范围等信息,利巴韦林滴眼液中苯扎溴铵的浓度仍有优化下降的空间,羟苯乙酯和硫柳汞钠在利巴韦林滴眼液处方中抑菌效力不满足要求或毒性较大,不适宜作为抑菌剂使用,建议优化处方更换更加适宜的抑菌剂。

Objective To evaluate the antimicrobial effectiveness of ribavirin eye drops for matching the general requirements of the 2020 edition of Chinese Pharmacopoeia(ChP)<1121>,and analyze the effectiveness of different kinds of antimicrobials with different concentrations for optimizing the prescription.Methods Three sample groups were investigated according to the antimicrobial effectiveness testing method in ChP,including 11 ribavirin eye drops,ribavirin solution without antimicrobials and antimicrobial solutions(benzalammonium bromide,hydroxyphenylate and thiomersal sodium).Results The antimicrobial effectiveness of ribavirin solution was fair on bacteria;however,it was not good enough on fungi.Apparently,it was necessary to add appropriate antimicrobial preservatives.The antimicrobial effectiveness of benzalkonium bromide solution(0.1 mg/mL)could meet the grade A standard;thiomersal sodium solution(0.006 mg/mL)could meet the grade B standard;but hydroxyphenylate solution(0.25 mg/mL)could not meet the grade B standard.Among the 11 samples of ribavirin eye drops,5 samples containing benzalammonium bromide could reach grade A,1 sample containing thiomersal sodium could reach grade B,and 5 samples containing hydroxyphenylate could not meet the requirements.Conclusion Based on our experimental data and information regarding the toxicity,commonly used concentrations,and limit values of the three antimicrobial preservatives,the concentration of benzalkonium bromide in ribavirin eye drops should be optimized and decreased.Hydroxyphenylate and thiomersal sodium were not suitable as antimicrobials in ribavirin eye drops,for they did not meet the requirements or had high toxicity.It was suggested to optimize the prescription by investigating the effectiveness and safety of antimicrobial preservatives.