Study On Formulation Technology And Quality Of Ornidazole Injection

Ornidazole is a new type of three generations of nitroimidazole drugs which are widely used in clinic after the presence of metronidazole and Tinidazole.Its principle is to transform nitro group into amino group without oxygen,or to break the helix structure of receptor in the way of free radical and block its transcription and replication.It has the advantages of quick effect,long acting time,general division,excellent tissue permeability,high cure rate,good curative effect and good safety.Its adverse reactions are much smaller than metronidazole and Tinidazole,so it has a good prospect of clinical development.In this study,we mainly studied the formulation process of ornidazole injection and the formulation of quality standards,and compared the original drugs,which can provide a more reliable production process for the factory production,also provide an effective quality standard,and also lay a favorable foundation for the application and registration of drugs.Objective:1.To screen the specification of ornidazole injection,the dosage of excipients,the range of pH value and sterilization temperature,and to carry out a small-scale test.2.High performance liquid chromatography was established for the determination of related substances and contents.3.To establish a gas chromatography method for the determination of ethanol and propylene glycol in excipients.4.Carry out quality research on three batches of small-scale test and formulate quality standards.5.Use small sample to study the influencing factors.6.The clinical compatibility of the samples was also studied.Methods:1.Optimize the formulation,take the properties,solution color,pH value,related substances,content,bacterial endotoxin,sterility,etc.as the inspection criteria,and study the influencing factors of the formulation to ensure that the optimal formulation and process can be determined.2.The main reference basis of the research method in this paper is the Chinese Pharmacopoeia(2015 Edition).High performance liquid chromatography(HPLC)was selected for the research and content detection of related substances.3.To study the quality of the small sample,including properties,identification,pH value,solution color,related substances,content,bacterial endotoxin,sterility,etc.,and to sort out the quality standard of ornidazole injection.4.The stability of the preparation was preliminarily determined by using small test samples to investigate the influencing factors.5.To study the clinical compatibility and stability of the small samples,the compatibility tests of sodium chloride injection and glucose injection were mainly carried out.Results:1.The specification,formulation and preparation process of ornidazole injection were determined:the specification was 0.5g/3ml,1g/6ml;the excipients were 270mg-330mg ethanol per 1ml,480mg-586mg propylene glycol;the pH range was 5.5-6.5;the sterilization condition was 121℃ hot pressing sterilization for 15min.2.The related substances of ornidazole injection were verified by methodology,and the content of ornidazole injection was determined by liquid phase detection method:C18 chromatographic column was used,the mobile phase was methanol:water(20:80),the flow rate was 1.0ml per minute,the detection wavelength was set to 318 nm,and the column temperature was 30℃.3.The quality standard of the product is formulated and the quality evaluation method is defined.4.Study on the influence factors of the small-scale test samples.The results show that under the condition of high temperature of 40℃ and high temperature of 60℃,the properties,solution color,pH value,related substances and content have no obvious changes,which are in line with the regulations;Under the condition of light,the impurities of photodegradation are produced,and the other test items have no obvious changes;under the condition of freeze-thaw test,the properties,solution color,pH value,related substances and content are not obvious change,in line with the regulations.The condition and stability of the sample were determined preliminarily.5.This product is compatible with sodium chloride injection and glucose injection,and can be stable within 2 hours.Conclusion:1.The best prescription and technology were determined,and the small sample was prepared.2.High performance liquid chromatography was used to detect the related substances and contents,and gas chromatography was used to detect the content of ethanol and propylene glycol,the results can accurately detect the data.3.The quality of self-made small test samples was studied.The results showed that the quality of three batches of small test samples with two specifications was stable and reliable.4.The influence factor test was carried out on the small test sample.Except for the increase of relevant substances under the light condition,there was no obvious change in the test properties,solution color,pH value,relevant substances and content under other conditions,indicating that the product had good stability and should be kept away from light during the placing process.5.The clinical compatibility test of the small sample shows that the compatibility stability of the product is good.