| As a brain-protecting medicine(free radical scavenger), edaravone can scavenge free radicals and inhibit lipid peroxidation, also can inhibit the peroxidation of vascular endothelial cells and nerve cells, delayed nerve cell death in brain and has curative effect of brain damage caused by ischemia.Edaravone is the first-line treatment to cerebral infarction in clinical treatment.Edaravone injection was developed by Mitsubishi Tokyo Pharmaceutical Co., Ltd.in Japan and the first time of marketing is in April 2001.It’s clinical safety and effectiveness has been widely recognized for its widely used in clinical practice.In china,Edaravone injection(20ml: 30mg) was first successfully developed by the Jiangsu Simcere and listed on in 2003. In recent years, there are another eight companies have approved the market, but sales of these listed companies are small volume injections(ampoules) Injection.In order to intravenous infusion, Edaravone small volume injection needs to be diluted by adding an appropriate amount of physiological saline solution before using. So, it is easy to increase the probability of contamination.Because of this situation, this project will study on large-capacity edaravone injection of sodium chloride(100ml: edaravone 30 mg sodium chloride 855 mg,soft pack), thus eliminating the need for pre-clinical use configuration process,avoid possible contamination in the configuration process, more convenient for using, provide precious rescue time for ischemic cerebral infarction.The purpose: study Earavone –sodium chloride injection prescription technology to ensure product quality and stability.Methods:1 Study on Preparation Process.1.1 imspect the impact of carbon adsorption to raw materials content Scheme I: the first using activated carbon to adsorb a containing materialssolution,。then filtering into the main drug and excipients; scheme Two: First put all the raw materials, and then use the activated carbon adsorption.Content of raw materials were detected under two schemes.1.2 diluted dosing’s p H range Effects of different p H(2.5,3.0,3.5,4.0,4.5,5.0) on sample quality.1.3 Selection of amount of added activated carbon The total amount of activated carbon were investigated by volume dilute with 0.01%(g/ml), 0.025%(g/ml), 0.05%(g/ml) addition on sample indicators.1.4 Select sterilization conditions Investigation by sterilized 12 minutes, 10 minutes in 121℃ and 30 minutes in 115℃ of three sterilization sterilization conditions, changes in sample index.1.5 Packing choice Three forms were studied respectively about sleeve jacket bags, seal sealed bag and evacuated bags2 Quality of edaravone sodium chloride injection Three pilot batches of products for the study, based on physicochemical properties and characteristics infusion formulation of earavone, to be determined by established HPLC related substances and content of edaravone,and methodological research; By influencing factor test and a six-month stability test, a preliminary understanding of the stability of the situation of the goods,providing the basis for determining validity for the production,packaging, storage, transport conditions.Result: Preparation Process Results Through investigation, determine preparation process of this product:Concentrated with: concentrated with adding Water for injection q.s. tank, into the calculated amount of sodium hydroxide, and sodium chloride was added,stirred to dissolve, an appropriate amount of activated carbon was added(by the total volume of diluted with 0.05% g/ml), stir, filtration, that was concentrated dosing.Dilute with cysteine hydrochloric acid was added in concentrated, stirring to dissolve, and adjust with phosphoric acid or Na OH solution to p H 3.5 to 4.5,then added edaravone, stirring to dissolve, then sodium bisulfite, stirred dissolution, additional water for injection to the whole amount, stir, to detect the component content and p H(adjusted with phosphoric acid or Na OH solution when necessary p H), filtration after qualified.After checking liquid clarity, nitrogen protection filling, sealing, vacuum sealed bags coat sleeve, 121℃ constant temperature sterilization 12 minutes,light inspection and packaging.2 Quality Study results:2.1 Three batches of test samples test results conform the relevant provisions of injection under Chinese Pharmacopoeia;2.2 Identity test proven good specificity;2.3 Using two liquid phases to inspect conditions related substances, method validation showed good specificity, high sensitivity, can effectively detect impurities present in the formulation.2.4 Using HPLC to test edaravone content verification showed that edaravone concentration showed a good linear relationship in the range of 0.15mg/ml~0.45mg/ml, repeatability RSD 0.28%, the recovery was in the range of98.04%~99.17%, RSD 0.05%.2.5 Stability study period, all indicat Sors are in line with the provisions of the preparation, quality and stability.Conclusion: The process parameters of the product is clear, reasonable and suitable for industrial production; quality standards established effective control of product quality; and through the influence factors on the stability of a six-month investigation, formulations of each index are in line with regulations. It provides a theoretical basis and reference to the quality standard of edaravone sodium chloride injection of and the expiration date. |
PDF Full Text Request