The Prescription Process Improvement Of Pefloxacin Mesylate Injection

Pefloxacin mesylate is the third generation broad-spectrum antibacterial activity of quinolones. The subcutaneous absorption of pefloxacin mesylate was satisfied. Pefloxacin mesylate could transfer blood-brain barrier, and no cross-resistance effects with other antimicrobial agents were found. However, pefloxacin mesylate is sensitive to light. The color of the pefloxacin mesylate injection would change from light yellow to reddish brown after exposed to strong light or to light for a long time. Thus, the color of the pefloxacin mesylate injection would be darker and darker and do not meet the national drug standards during transport if exposing to the strong light for a long time. Therefore, the improvements on the formulation and the process paramers of are needed to keep the quality of the pefloxacin mesylate injection and ensure the patients' safety.On the basis of the references and the analysis of the influence factors on the stability of the pefloxacin mesylate injection, we carried out the corresponding studies by chosing the category as well as the quatity of the oxidation inhibitors, the adjusting of the pH of the pefloxacin mesylate injection, and so on to improve the stability of the pefloxacin mesylate injection. The formulation and the process parameters were optimized and the stability of the obtained pefloxacin mesylate injection was satisfied and met the stardards of the Chinese Pharmacopeia.The main studies were as follows:Firstly, the determination method of the pefloxacin mesylate contents and the related substance of the pefloxacin mesylate injection were founded according to the stardards of the Chinese Pharmacopeia. The high performance liquid chromatography method was established using octadecyl silane bonded silica colomn, the mobile phase was potassium dihydrogen phosphate-0.05 mol/L tetrabutylammonium bromide solution-acetonitrile(80:8:9)(pH4.0 adjusted with phosphoric acid), the main peak was detected at 12 minutes. The suitability test, the minimum detectable amount of the method, the minimum quatity amount of the method, the precision of the method, the linear relationship between the spectral peak area and the sample concentration, and the recovery experiments were all verified the method was feasible and reliable. The separation of the related substances and pefloxacin mesylate was satisfied.The quality of raw pefloxacin mesylate showed great influence on the quality pefloxacin mesylate injection. The needle crystal could be observed in the pefloxacin mesylate injection if the raw material was not purified. So the raw materials need to be refined and purified, and the purity of the raw pefloxacin mesylate was expected to reach at least 99%.It was found that sodium metabisulfite was the best antioxidant agent. Natrium bisulfurosum was selected at last for the irritating side effect of sodium metabisulfite. The results of the comparative studies indicated that 0.1% natrium bisulfurosum worked pretty well to ensure the stability of the pefloxacin mesylate injection.To fill nitrogen during filling process could reduce the residual oxygen inside the ampoule bottle, thus filling nitrogen could resist oxidation of pefloxacin mesylate. The improved nitrogen filling process could improve the stability of the injctions and the following were the optimized formulation and the process parameters:thenatrium bisulfurosum dosage was set at 0.1%, the concentration of activated carbon was 0.1%, the pH was 3.0～5.0, the sterilization tempreture was 115℃and the sterilization needed to keep for 30 minutes.The content of pefloxacin mesylate decreased and the conconts of the related substances increased slightly after exposed to light for 10-day according to the results of the stability studies. The color of the injections was a bit deeper. While, the content as well as the related substances still met with the requirements. The similar results were obtained from the accelerated test at 40℃for 6 months. No changed indexes were observed in the investigation of the long term test, including the sample characteristics, pH, clarity, color, content, and the related substances.Thus, the optimized formulation and the process parameters were satisfied and the goal of the studied was realized.