Preparation And Pharmacological Toxicology Of Enrofloxacin Mesylate Soluble Powder

Enrofloxacin is a special antibacterial agent for animals.It is a chemically synthesized third-generation fluoroquinolone broad-spectrum antibacterial agent.It has excellent antibacterial effect and is widely used in clinical practice.However,the solubility of enrofloxacin is extremely low,which greatly limits its clinical use.Enrofloxacin is an amphoteric compound,and the preparation of enrofloxacin mesylate in this laboratory greatly improved its solubility.In combination with the need for large-scale aquaculture,this study used soluble powder as the dosage form to compare the prescription screening,preparation process,quality evaluation,pharmacodynamics,acute toxicity and pharmacokinetics of enrofloxacin mesylate soluble powder.Systematic research has achieved the intended research objectives.1.Taking the hygroscopicity,agglomeration rate,enrofloxacin mesylate content change,solubility,fluidity and taste masking effect as indicators,the effects of fillers,glidants and flavoring agents on the quality of the preparation were investigated.Factor experiment to screen the prescription composition of enrofloxacin mesylate soluble powder,and finally determine the prescription of enrofloxacin mesylate soluble powder:20%enrofloxacin mesylate,0.25%menthol,0.5%Sorbitol,a filler with super lactose.2.The quality of enoxacin mesylate soluble powder was studied from the aspects of character,identification,examination and content determination,and the quality standard draft of enoxacin mesylate soluble powder was established.The results confirmed that enoxacin mesylate soluble powder was a white granular solid powder.The identification of mesylate and enoxacin in Chinese pharmacopoeia,HPLC and ir were used to identify mesylate and enoxacin respectively.The inspection contents of the preparation are as follows:uniformity of appearance,dryness,weight loss and solubility;the appearance of the preparation is determined to be uniform without obvious impurities such as patterns;Drying weight loss is 2.13%,which meets the requirements;The results of solubility test were in accordance with the requirements of Chinese veterinary pharmacopoeia.The in vitro assay method was used to determine the content of enoxacin mesylate soluble powder 84.56%.At the same time,the stability of enoxacin mesylate soluble powder was preliminarily studied.The change of drug content was 4.52%.3.The pharmacodynamics,acute toxicity and pharmacokinetics of enoxacin mesylate soluble powder were studied.The results of in vitro antibacterial experiments showed that compared with enoxacin mesylate soluble powder,the MIC values of several common clinical tested bacteria were all within the range of 0.059³.125?g/mL,and there was no significant difference between the same tested bacteria groups,indicating that enoxacin mesylate did not affect the antibacterial effect of enoxacin.In addition,in the in vivo pharmacodynamics study of mouse escherichia coli infection model,in the cure rate results,enoxacin mesylate soluble powder and enoxacin hydrochloride?5 mg/kg?were 50%and enoxacin?5 mg/kg?were 40%in the medium dose group,with no significant difference.However,in the results of relative weight gain rate,the soluble powder of enoxacin mesylate in the medium dose group was85%,slightly higher than enoxacin hydrochloride?83%?and enoxacin?74%?,indicating that enoxacin mesylate did not affect the therapeutic effect of the drug and showed some improvement.In acute toxicity test,the oral LD₅₀ of enoxacin mesylate soluble powder?measured by enoxacin?on mice was 929.744 mg/kg,and the 95%confidence limit was771.190 mg/kg¹146.063 mg/kg.In SD rats in the animals,oral medicine 5 mg/kg?the effect of project?to one for studying the in vivo pharmacokinetics,the results showed that the er effect of soluble powder and the er nuo mesylate,hydrochloric acid,characters and pharmacokinetic data are conform to the level of absorption effect of 2 rooms open model,mesylate well,the main pharmacokinetic parameters of soluble powder as follows:Cmax was0.793±0.231 mg/L,Tmax was 0.917±1.053 h,AUC?0-t?was 4.845±1.235 mg/L*h,t1/2?was 1.458±1.142 h,t1/2Ka was 0.587±0.592 h and AUC?0-??was 5.119±0.934 mg/L*h.AUC?0-t?and AUC?0-??were significantly greater than enoxacin and enoxacin hydrochloride,indicating a higher bioavailability of enoxacin mesylate phase.This project successfully developed enrofloxacin mesylate soluble powder,the preparation process is simple,the flavoring effect is good,the quality is controllable,and the quality standard is feasible.In addition,the enzymatic effect of enrofloxacin mesylate soluble powder is better,it can effectively treat the infection caused by sensitive bacteria,and the relative bioavailability is significantly improved;and the oral LD50 of mice has not changed significantly,which proves that the soluble powder selected excipients It is safe and non-toxic,and the toxicity of the drug is not increased after the preparation.This study provides a new preparation of enrofloxacin with good solubility and ease of use,and also provides a new idea for the innovation of enrofloxacin preparation.