Development Of Compound Doxycycline Hydrochloride Oral Liquid

Doxycycline Hydrochloride and Telmicocin Phosphate were combined.The dosage of excipients and the formula of Compound Doxycycline Hydrochloride Oral Liquid were determined by orthogonal experiment.Then pharmacodynamics was studied from four aspects:quality control test,establishment of content analysis method,in vitro bacteriostatic experiments test and acute toxicity test,to provide reference for veterinary clinical drug use.1.Preparation and quality controlThe excipients of the preparation were screened through pre-test,the prescription was optimized by orthogonal test,finally the formula of compound Doxycycline Hydrochloride Oral Liquid was determined.In terms of quality control,the clarity,pH and stability of the preparation were investigated.The test results showed that the optimal formula was 10 g Doxycycline Hydrochloride,10 g Tilmicosin Phosphate,2 mL Phosphmporic acid,6 g Magnesium chloride,0.2 g Sodium thiosulfate and 5 mL Tween 80 per 100 mL of compound Doxycycline Hydrochloride Oral Liquid.The preparation is light brown with good clarity and no insoluble substances visible to the naked eye.The pH range is 4.0-4.3,which meets the requirements of the Pharmacopoeia for oral liquid preparations.It has good stability,which can be preserved for a long time,but it is susceptible to strong light and high temperature.Therefore,it should be preserved at room temperature and away from light.2.Establishment of content analysis methodThe content analysis method of Doxycycline Hydrochloride and Tilmicosin Phosphate is established by HPLC and LC.The results showed that the linear relationship of Doxycycline Hydrochloride was good in the concentration range of 50-300μg/mL.And Timicocin Phosphate has a good linear relationship in the concentration range of 200-1000μg/mL.At the same time,the recovery,repeatability and precision of the method were tested,which were in accordance with the provisions of the Pharmacopoeia.The test results showed that the method was accurate and reliable.3.In vitro bacteriostasis testMIC,MBC and FIC of Doxycycline Hydrochloride and Tilmicocin Phosphate against Escherichia coli,Staphylococcus aureus,Salmonella Typhi,Pasteurella multocida and Streptococcus agalactiae were determined by in test tube double dilution method and micro chessboard dilution method.The MIC of Doxycycline Hydrochloride is 4-32μg/mL,the MIC of Tilmicosin Phosphate is 4-16μg/mL.The MBC of Doxycycline Hydrochloride is 8-64μg/mL,and the MBC of Tilmicosin Phosphate is 8-32μg/mL,indicating that the preparation has good antibacterial effect.The results of combined drug sensitivity test show that the combined use of the preparation has a good positive effect,which can enhance the bactericidal effect of bacteriostatic.4.Acute toxicity testThe LD₅₀ of Compound Doxycycline Hydrochloride Oral Liquid on mice was 1541.7mg/kg by Simplified Cooley method,the trusted limit of LD₅₀ 95%is 1194.2²269.5 mg/kg.According to the grading standard of acute toxicity of the oral who compound,the drug is a low toxicity drug.5.SummarizeCompound Doxycycline Hydrochloride Oral liquid was prepared by the combination of Doxycycline Hydrochloride and Tilmicosin Phosphate.After screening the optimal formula,the quality control is carried out.Finally,the Compound Doxycycline Hydrochloride Oral Liquid with viscous light brown and good stability was clarified.The pH of the preparation meets the requirements of oral liquid and has high stability,but is sensitive to strong light and high temperature.Therefore,the light should be avoided and preserved at room temperature.In vitro bacteriostatic test results showed that the preparation had good bacteriostatic effect,and its LD₅₀ was 1541.7 mg/kg,which was a low toxicity drug with high safety.