Characterization Of Florfenicol Cocrystal And Its Pharmacokinetics Studies In Pig

As a member of the chloramphenicol family,the antibacterial spectrum of florfenicol and thiamphenicol is similar,which has high antibacterial activity against Leptospira,Rickettsia,Mycoplasma,most of Gram-negative bacteria and Gram-positive bacteria,and the antibacterial activity of florfenicol is superior to other chloramphenicol drugs.Florfenicol has been widely used for the treatment of a variety of animal bacterial diseases in clinic.In the past few years,as a new class of solid drugs,the research of drug cocrystals has attracted wide attention.On the basis of not changing the activity of the drug,the structural changes of pharmaceutical cocrystals,which significantly improved the drug solubility and dissolution rate,at the same time,pharmaceutical cocrystals can also enhance the physical stability and chemical stability of active pharmaceutical ingredients.The quality evaluation and characterization of the prepared florfenicol co-crystal were studied in this paper.X-ray diffraction results show that the crystalline form of florfenicol changed significantly,indicating that the florfenicol co-crystal is a new crystalline state material.In this study,the stability and solubility of the crystals were investigated by influencing factors.The results showed that the stability of florfenicol co-crystal was good in the high temperature,high humidity and strong light conditions,the content and solubility did not change significantly.The saturation solubility test results showed that the saturated solubility of the florfenicol co-crystal at normal temperature was increased to 1.75mg/mL from 1.50 mg/mL.A highperformance liquid chromatography method was developed for the determination of the content of florfenicol co-crystal and florfenicol in pig plasma.The limit of detection and limit of quantification were 0.05?g/mL and 0.1?g/mL,respectively.For the detection of the content of florfenicol co-crystal,the mean recovery was 98.65%,and the intra-day and inter-day relative standard deviations were less than 2%.For the determination of florfenicol in pig plasma,the correlation coefficients were greater than0.999 over a dynamic range of 0.5⁵0?g/mL,the limit of detection and limit of quantification were 0.05?g/mL and 0.1?g/mL,respectively.The mean recoveries of target compounds obtained for low,middle,high spiking levels were 92.83%,and the intra-day and inter-day relative standard deviations were less than 3%.Twelve healthy and hybrid pigs?20.98±2.0 kg,60 days?were randomly divided into two groups,the florfenicol co-crystal and florfenicol powder were intragastrically administered at a dose of 30 mg/kg b.w..The main pharmacokinetic parameters were determined by means of the WinNonlin 5.2.1 corresponded to the noncompartmental pharmacokinetic model.The main pharmacokinetic parameters of florfenicol co-crystal and florfenicol powder were as follows:t1/2?14.92±0.92 h,10.68±0.35 h;t_max 5.67±0.82 h,1.42±0.20 h;C_max 21.55±0.65?g/mL,21.16±0.45?g/mL,AUC_0-last 251.89±6.79?g·h/mL,185.05±3.90?g·h/mL;MRT 11.67±0.02 h,7.30±0.06 h.The main pharmacokinetic parameters were analysed by SPSS software,the results indicated that t_max,t1/2?and AUC_0-last of florfenicol co-crystal were significantly increased,MRT were significantly prolonged,the statistical differences were significantly?p<0.01?.The results showed that compared with florfenicol powder,the florfenicol co-crystal had a slow-release effect and eliminated relatively slowly,and significantly improves the bioavailability of florfenicol.