ABSTRACT
OBJECTIVE: To discuss the role of proficiency testing program for pharmaceutical dissolution determination in the capacity building of relevant laboratories. METHODS Based on the results of the two proficiency testing programs carried out in recent years, analyze the difference of the quality management and the level of dissolution determination among the participating laboratories and discuss on the way that the proficiency testing programs carried out in future. RESULT: There is difference among the laboratories in both the quality management and the level of dissolution determination, the "unsatisfactory" laboratories mainly concentrated in local drug control institutes and pharmaceutical manufacturers. The three "unsatisfactory" laboratories in the first program, took corrective and preventive measures, participated in the later program, and achieved "satisfactory" results. CONCLUSION: The proficiency testing program is effective in improving the dissolution determination capacity of the participating laboratories and is recommended to be conducted continually in the pharmaceutical industry.
ABSTRACT
The paper reports the systematic study on felodipine and its impurities in tablets, to improve its quality standards for the control of the related substances. HPLC-DAD, UPLC-MS, IR and NMR methods were used for the isolation of felodipine and its impurities in tablets, their identification and the zebrafish animal model was used for the analysis of the toxic impurities. In felodipine material and its tablets, three impurities are isolated and identified. They are impurity 1 [dimethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], impurity 2 [ethyl methyl 4-(2, 3-dichlorophenyl)-2, 6-dimethylpyridine-3, 5-dicarboxylate] and impurity 3 [diethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], separately. The result of zebrafish animal model analysis showed that the teratogenic effects of four compounds were: impurity 3 > or = felodipine > impurity 1 > impurity 2, lethal effects were as follows: impurity 2 = impurity 3 > felodipine > or = impurity 1. This study confirmed the toxicity of three impurities in felodipine. According to the results, the paper suggested the amendments to the standard of the medicine and provided the support to the control of impurities in the manufacturing process.