The Quality Control And The Study Of Quality Standard For Compound Benzocaine Gel

Objective: Compound Benzocaine Gel is compose of Benzocaine,Benzalkonium Chloride and Zinc Chloride,is the new pharmaceutic preparation medicine(dosage form)for oral.In order to the using secure of patients and effectiveness of the products,for improving the effective control of the quality of products,subject carry on a system research for benzocaine and Compound Benzocaine Gel on related substances、determination of content and Microbial limit test and other projects.The subject formulated the quality of standard of medicines,established a complete quality system from the quality control of raw materials and subsidiary materials to quality assurance of preparation to the constantly monitoring of products for later stability.Methods: Method of HPLC was used to check Benzocaine’s related substances,the experiments explored the impurity instructions through destructive test,identified the related impurity using reference substance.Study on methodology for determination of Benzocaine,its related substances and Degradation products was performed with HPLC.And contrast test was checked by comparing with pharmacopoeia method.According to the general principles of Chinese Pharmacopoeia(edition 2015),experiments carried on inspection studies for Compound Benzocaine Gel on character,identification,related substances,determination of content and other projects.The distinguish studies of Benzocaine,Benzalkonium Chloride and Zinc Chloride in Gel were conducted with UV Spectrophotometry,HPLC,Colorimetry,Chemical method by separately.The Method of HPLC was established for the determination of Benzocaine and its related substances in gel,method of AAS was applied for the determination of Zinc Chloride,method of HPLC was used in the determination of Benzalkonium Chloride.All the method had proceeded the methodological study.According to the general principles of Chinese Pharmacopoeia(edition 2015),operational test of methodology was performed respectively by routine method,neutralization method,dilution and neutralization method.By comparison with recovery ratio of test bacteria,the medium of dilution and neutralization was adopted in total aerobic microbial count,total combined yeasts and molds count,the neutralization method was adopted in control bacteria.Neutralizing agents were polysorbate80 and lecithin.Results: The Main active components,Benzocaine in Gel could be identified from dosage form by UV and HPLC;the other active components,Zinc Chloride could be distinguished by feature by Chemical method.Benzocaine may be degraded under the condition of acid and alkali,its degradation was slower in acidic conditions and faster in acidic conditions.The degradation product is 4-aminobenzoic acid.Benzocaine content and its related substances in material and preparation were determined concurrently by HPLC,chromatographic conditions were the same,the chromatographic peak of Benzocaine and its related substances(4-aminobenzoic acid)were completely separated,other components and accessories did not affect the measurement.The calibration curve of Benzocaine was linear in the range of 5.08~127.0μg/ml,the average recovery of 80%,100%,120% concentration were 98.94%、99.55%、99.41% respectively,RSD were 1.32%、0.94%、1.09%.Zinc Chloride content in preparation was determined concurrently by AAS.The calibration curve of Zinc Chloride was linear in the range of 0~2.0μg/ml,the average recovery of 80%,100%,120% concentration were98.89%、98.53%、98.02%respectively,RSD were 1.28%、1.15%、1.21%.All the methods were stable,accurate with good reproducibility.The method of dilution and neutralization could eliminate the inhibition of the drug,recovery ratio of each test bacteria were in the range of 0.5~2.0 and in line with Chinese Pharmacopoeia 2015.Escherichia coli and Pseudomonas aeruginosa and Staphylococcus aureus could be detected in the positive control bacterial test,and negative bacterial were not detected.Conclusion: According to the studies,we had confirmed the monitoring indexes of related substances in raw materials and preparations.Internal control quality standard of Benzocaine and Compound Benzocaine Gel were drew up accordingly.The integral quality control system of Compound Benzocaine Gel were established and could be used for the effective control of quality.