Development Of Cotrimoxazole Injection

Sulphonamides and antibacterial synergists have been used to this day because of their low price and broad antibacterial spectrum.When sulfamethoxazole and Trimethoprim are used in combination,the metabolism of bacteria can be doubly blocked,which can not only reduce the amount of drugs used,but also enhance the antibacterial effect several times to dozens of times,reduce the toxic side effects of drugs and improve the safety of clinical use.In this study,Sulfamethoxazole and Trimethoprim were combined to prepare the compound Synthroid injection by screening the excipients and optimizing the prescription through L9(3~4)orthogonal test.It was investigated from four aspects:prescription screening and quality control,establishment of main drug content determination method,pharmacodynamic test and safety evaluation.In order to provide theoretical support for the clinical use of cotrimoxazole injection.1.Preparation and dose control of cotrimoxazole injectionThe excipients were screened by pre-experiments and the prescription was optimized by L9(3~4)orthogonal test to determine the best formulation of cotrimoxazole injection,which was investigated for appearance,colour and clarity of solution,p H,thermogenicity and stability.The results showed that each 1000 m L of cotrimoxazole injection contained 100 g of sulfamethoxazole,20 g of trimethoprim,45%organic reagent content,3 g of sodium metabisulphite and 30 m L of polyethylene glycol-400(PEG-400).The injection is pale yellow,clarified,with no visible foreign matter,p H around 8.0 and no pyrogenic reaction.Stability studies have shown that the injection is stable but needs to be stored in a brown light-proof bottle.2.Establishment of a method for the determination of the content of cotrimoxazole injectionA method was selected for the determination of the content of two main drugs in cotrimoxazole injection,and the precision and stability of the method were investigated.The results showed that Sulfamethoxazole was determined to be linear in the range of 3-15μg/m L at 257 nm with a reference wavelength of 304 nm using dual wavelength UV spectrophotometry at the same absorption point.The linearity of Trimethoprim was determined at 239 nm with a reference wavelength of 295 nm in the range of 4-15μg/m L.The RSDs of the recovery test and precision test for the two main drugs were less than 1%.The test method has good precision,accurate and reliable results.3.pharmacodynamic studiesThe MIC of sulfamethoxazole,trimethoprim and cotrimoxazole injection to four strains,the MBC of compound sulfamethoxazole injection to Escherichia coli,Staphylococcus aureus,Salmonella and Pasteurella multocida were determined by test tube double dilution method,and the inhibitory concentration index(FIC)of four strains was determined by micro chessboard dilution method.The results showed that the MICs of sulfamethoxazole against the four bacteria were 64,128,256 and 128μg/m L respectively;the MICs of Trimethoprim against the four bacteria were 32,128,64 and 32μg/m L respectively;the combined drug sensitivity test showed that the combination of the two was synergistic against Escherichia coli and Salmonella,and additive against Staphylococcus aureus and Pasteurella multocida,yielding The MIC of compound Xinomin injection against the four strains were 8,32,16 and 32μg/m L respectively;the MBC were 16,128,32 and 64μg/m L respectively,concluding that the prepared cotrimoxazole injection cotrimoxazole injection had certain antibacterial and bactericidal effects against the four strains.4.Safety evaluationThe safety of compound sulfamethoxazole injection was evaluated by acute toxicity test,muscle irritation test in rabbits and systemic allergy test in guinea pigs.The results showed that in the acute toxicity test,the LD50 of cotrimoxazole injection was 3172.74 mg/kg,and the 95%confidence limit interval of LD50 was 2665.38 to 3828.79 mg/kg.According to the classification criteria of drug toxicology,cotrimoxazole injection met the low level criteria and had a good safety profile.The results of the muscle irritation test in rabbits indicate that the injection is not muscle irritating and can be used for intramuscular injection.The result of systemic allergic reaction was negative,and there was no obvious allergic reaction.Conclusion:The test results showed that the cotrimoxazole injection prepared by the combined formulation of sulfamethoxazole and Trimethoprim,after prescription screening and quality control,yielded a cotrimoxazole injection with a light yellow appearance,clarification,no visible foreign matter,p H around 8.0 and no pyrogenic reaction,which is stable but sensitive to light and needs to be stored in a brown light-proof bottle.After pharmacodynamic tests and safety evaluation,the injection has good antibacterial and bactericidal effects,no intramuscular irritation can be used for intramuscular injection.It is a low toxicity drug with good safety.