| [Objectives]Formulation process of 20%tylosin base injection were developed to obtain 20%tylosin base injection with good stability,and the content,properties,and pH value all met the requirements.Established quality standards to control and evaluate the quality of preparations,and its irritation to rabbit muscle and pharmacokinetic characteristics in vivo were studied,in order to provide basis for further clinical use of and application of new veterinary drugs.[Methods]1.The organic solvent,temperature and ph value were screened by single factor test,and the prescription was optimized by the orthogonal test;The stability of the preparation was investigated by influencing factor test,accelerated test and long-term test,and the investigation index included content,traits and pH value.2.A high performance liquid chromatography method for content determination was established and verified,as well as the character and pH value of self-developed tylosin base injection were observed,and then the quality criterion of 20%tylosin base injection was preliminarily formulated.3.Four healthy rabbits were used to investigate the muscle irritation of 20%tylosin base injection by left-right control method in the same body.4.The pharmacokinetics of 20%tylosin base injection in eight healthy rabbits were studied by using HPLC external reference method and 3P97 software was used for pharmacokinetic data analysis.All rabbits were injected tylosin base injection at a single dosage of 30mg/kg b.w by intramuscular,and then the drug concentration in plasma via auricular vein at different time were detected.[Resultes]1.The best prescription parameters of 20%tylosin base injection including 20%tylosin base,50%Propylene Glycol and water.The process was to accurately weigh 20g of tylosin base API,dissolved it in 51.75g propylene glycol at 60℃,set the volume of water for injection to 100mL,and adjust the pH value to 9.5 with 20%sodium hydroxide solution.The stability test results show that the preparation should be packaged in brown bottles and transported and stored below 30℃.2.The chromatographic conditions of HPLC method were as follows:the analytical column was X-bridgetm C18(4.6mm ×250mm,5μm particle size),the mobile phase was 0.05M naclo4(adjusted to pH of 2.5 with 1M Hcl)acetonitrile(65:35,v/v)at a flow-rate was 1.0 mL/min.Tylosin was detected at 290nm and at a column temperature 35℃,and the 20μL was injected into HPLC system.A good linear relationship was found in the range of 49-298μg/mL.The linear regression equation was Y=0.3882X+0.1103(R2=0.9996),and the RSD values of recovery,repeatability,intra-day,inter-day were less than 2%.It indicated that this method was accurate and reliable to detect the content of tylosin base injection,and the content range was 99%～105%;The character was faint yellow clear liquid and pH value was 8.5～10.0.3.The results showed that the muscle stimulation level of tylosin base injection was "slightly",and swelling and necrosis were not observed.The tylosin base injection was safe for animals,it was meeting the criteria of intramuscular injection and suitable for intramuscular injection in veterinary clinic.4 The results indicated that the pharmacokinetic characteristics of tylosin base injection in vivo were fit for two-compartment model with a weight coefficient as 1/C/C.The pharmacokinetic equation was C=6.03e-0.37t+0.14e-0.01t.The main pharmacokinetic parameters were as follows:Tpeak was 1.04±.025h,Cmax was 3.16±1.10 μg/mL,t1/2 β was 57.04±5.90h,V/f was 7.44±3.21 and AUC was 31.19±5.28 μg/mL.h,apart.[Conclusions]The formula of self-developed tylosin base injection has stable process,good repeatability,and little irritation to animals.The established quality standards can carry out more comprehensive quality control of the product.Tylosin base injection can be quickly absorbed after i.m.Administration,and the efficacy of the pharmaceuticals was maintained for a long time,and dosing intervals of 24 hours was recommended. |
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