Pharmaceutical Research And Preclinical Safety Evaluation Of A Freeze-dried Tigecycline Injectable Powder

This application without excipient of Tigecycline for injection,which meets the requirements of safety,stability and controllability,is developed in order to avoid the disadvantages of commercially lactose.The production process,specification and stability of Tigecycline for injection are studied systematically.And the drug’s safety is evaluated preliminary.In this study,we confirmed the clinical using Tigecycline in injecting without lactose,which lays the foundation of Tigecycline industrialization and marketing in future.This paper provides a commercial process for the preparation of Tigecycline freeze-dried powder for injection.0.067% antioxidant is added to the sample solution which kept by edetate disodium,and the p H value close to neutralization.The freeze-drying stage costs 38 hrs without nitrogen protection.The intermediate of product should be quickly cooled to-45℃ at pre-freeze stage,and then hold for 1h at this temperature.Heat the frozen product back to-20℃,and hold for 2 hrs.Cool to-45℃ slowly and hold for 2 hrs.In next time,there are 3 steps in sublimate-drying,which heated from-45℃ to 0℃ over a period of 21.5 hrs.After that,desorption drying takes 7 hrs from 0℃ to 45℃.The character,identification and examination of Tigecycline for injection are studied in detail.The draft of specification is established.It is proposed that the single maximum impurity of related substances is less than 2.5%,the total impurities is less than 3.0%,and the content of the Tigecycline(C29H39N5O8)is to be 90%~110%.The drugs are stable and controllable by test with these standards.In this paper,the stress testing,accelerated and long-term stability tests are carried out on Tigecycline for injection.The results show that there are no obvious changes in each stability test.The formulation,preparation and storage conditions can ensure the Tigecycline for injection is stable in quality.Stimulation on blood vessel,hemolysis relating to the Tigecycline for injection are evaluated in rabbits.Active systemic anaphylaxis test in Guinea pigs and passive cutaneous anaphylaxis test in rats are also studied.The result shows that there is no stimulation on blood vessel of rabbit,no hemolysis or agglomeration on red blood cells in vitro of rabbit,and no allergic action on Guinea pigs and rats.All above proves that this drug is safe for clinical application.