Preparation And In Vivo/in Vitro Release Of Florfenicol Solid Dispersion

Because of Florfenicol(Florfenico,FF)poor water solubility,the clinical application is extremely inconvenient.This article aims to improve the solubility and bioavailability of florfenicol by preparaing florfenicol amorphous solid dispersion(FF-ASD).Select HPMCAS-HF,HPMCAS-MF and HPMCAS-LF were selected as carriers,and FF-ASD was prepareed by anti-solvent co-precipitation method.The X-ray diffraction peak intensity,position and number of changes were used to preliminarily identify the generation of new substances.Thermal weight loss and differential calorimetry scanning were used to analyze the melting point,crystal form transition and decomposition temperature of the sample.Dissolution in pH 6.8 phosphate buffer solution was tested as an indicator to screen and optimize the optimal FF-ASD.Then the FF-ASD was characterized through Fourier infrared spectroscopy to investigate whether there is intermolecular force and absorption peak coverage between the drug and the carrier.Scanning electron microscope was used to observe the morphological structure and particle size changes of the drug.The saturated solubility and the dissolution rate of FF-ASD were compared by measuring the dissolution in the pH 1.2 hydrochloric acid solution and the pH 6.8 phosphate buffer solution.The stability of FF-ASD was evaluated by X-ray diffraction by testing whether there was a crystal diffraction peak under 25℃ and 6 different relative humidity for 3 months.The 817 broilers were administrated with florfenicol and the FF-ASD respectively to get pharmacokinetic parameters.Blood was collected at a fixed time point and the blood drug concentration was determined by HPLC.The results showed that eight FF-ASDs were successfully prepared by using co-precipitation technology to separate FF with HPMCAS-HF,HPMCAS-MF and HPMCAS-LF.Three kinds of solid dispersions,namely FF-HF ASD(FF:HF=4:6),FF-MF ASD(FF:MF=5:5)and FF-LF ASD(FF:LF=4:6),were screened out.The particle size of FF-HF ASD and FF-LF ASD are nanometer.In the X-ray powder diffraction pattern,the FF have obvious diffraction peaks,and none of the three carriers have obvious diffraction peaks.No crystal diffraction peaks were seen in FF-HF ASD,FF-MF ASD and FF-LF ASD,indicating that the three polymers and drug FF were all formed to solid dispersions.In the thermal analysis chart,a sharp absorption peak of FF can be seen at 154.96℃,and there is no endothermic peak for the three carriers during the heating process.The crystal melting peak of FF in FF-HF ASD,FF-MF ASD and FF-LF ASD all disappeared completely.It can be seen from the scanning electron microscope that the particle size of FF-HF ASD and FF-LF ASD are both smaller than 500 nm,and the particles are uniform.In the in vitro dissolution,the dissolution effect of FF-HF ASD,FF-MF ASD,and FF-LF ASD in pH 1.2 hydrochloric acid solution were poor or even lower than that of FF.In pH 6.8 saturated phosphate buffer solution,the saturated solubilities of FF-HF ASD,FF-MF ASD and FF-LF ASD were 2.91,5.55 and 7.57 mg/mL,respectively,which were 2.5,4.8 and 6.6 times higher than that of original FF drug(1.15 mg/mL).The stability results showed that the FF-HF ASD under(25±5)℃,the properties were stable within 3 months below(55±3)%humidity,also stable within 1 month below(75±3)%humidity;FF-MF ASD was stable within 3 months under(25±5)℃ and(75±3)%humidity;FF-LF ASD was stabel under(25±5)℃ and(85±3)%humidity within 3 months in nature,and 1 month under(95±3)%humidity.The results of broiler pharmacokinetics showed that the peak time of FF-HF ASD,FF-MF ASD and FF-LF ASD was significantly shorter than that of FF bulk drug(P<0.01).The maximum plasma concentration of FF-MF and FF-LF ASD were significantly increased(P<0.01),which were 1.54 and 1.45 times than FF,respectively.The bioavailability of FF-HF ASD and FF-LF ASD were increased by 30.6%and 36.7%,respectively.It can be seen that FF-HF ASD,FF-MF ASD and FF-LF ASD can effectively improve the solubility and in vitro dissolution rate of FF,and FF-HF ASD and FF-LF ASD can improve the bioavailability of the poorly soluble drug FF.