The Studies On Fomulation And Stability Of Ornidazole And Sodium Chloride Injection

Ornidazole, a third generation of nitroimidazole antibiotic, was used to treat a variety of diseases caused by anaerobic bacteria such as bacteroides in clinical. Comparing with metronidazole and tinidazole, ornidazole was safe and effective with the advantage of higher permeability and less side effects. It has great potential for developing and used in clinical. In this study, investigation of the formulation and preparation process and stability of ornidazole and chloride sodium injection was carried out. The quality standard of the ornidazole and sodium injection was also investigated for industrialization of the product to ensure the quality of the products. This research would provide an opportunity for the approval of the registration.Objective:1 Establish the high performance liquid chromatography (HPLC) analysis method for determination of the content of the drug and the related substances.2 Screen the specification of ornidazole and sodium chloride injection, amount of activated carbon, pH value range and sterilization temperature and carry on the pilot-scaled production.3 Evaluate the quality of pilot-scaled products, including the pH value, the related substances, the color, the soluble particles, the visible foreign matter, the osmotic pressure molar concentration, heavy metals, sterile, bacterial endotoxin, loading and so on.4 Investigate the stability of the samples.Methods:1 The content of ornidazole and the related substances were determined by HPLC according to the method in Chinese Pharmacopoeia.2 The formulation of the sample was utilized by factorial design. The color, pH value, content, the related substances, endotoxin, bacteria and other indicators were evaluated.3 The quality standard of ornidazole and sodium chloride injection was established through the evaluation on the characterization of the products, including color, pH value, content, the related substances, endotoxin, sterile and heavy metals.4 The influence factor test, acceleration test and long-term stability test of the samples were investigated for the stability of the products.Results:1 HPLC method was determined for the measurement of ornidazole and the related substances; ostade-cylsilane was chosen as filler, mobile phase:methanol:water: glacial acetic acid (30:70:0.2); flow rate:1.0 ml/min; the detection wavelength was 318 nm. The feasibility of the method was verified.2 The specifications, fomulation and preparation method was determined. pH ranges from 3.0 to 4.5.0.01% (w/v) of activated carbon was chosen as the optimal amount. The sterilization condition was 121℃ for 15 minutes.3 The quality standard was determined for the product, and the evaluation methods of quality were established.4 Influence factors, acceceleration and long-term stability test of the omidazole and sodium chloride injection were carried out.Conclusion:1 It is feasible to use high performance liquid chromatography to deter mine the content of ornidazole and sodium chloride injection and the related substances. 2 Ultimately, the optimum formulation and manufacturing process was determined, the pi lot-scale test was conducted. The quality research of the three batches trial products show ed that the pilot production was stable and reliable, and could meet the clinical needs.3 T he pH value, related substance, color of the solution, soluble particles, visible foreign mat ter, osmotic pressure molar concentration, heavy metal, sterile, bacterial endotoxin, quant ity of the three batchs of trial products met thequantity standard.4 Influence factors, accel eration and long-term stability test of the ornidazole and sodium chloride injection were c arried out. Tthe results showed the injection was stable.