Tilmicosin Gelatin Microcapsule Excipients,Impurities And Non-clinical Pharmacokinetic Studies

Tilmicosin is an animal-specific antibiotic with broad antibacterial spectrum and good pharmacokinetic characteristics.In order to cover up its bad taste and increase its bioavailability,tilmicosin gelatin microcapsules were prepared in our laboratory.Excipient screening test,impurity determination test,and pharmacokinetic studies of single and multiple administration of tilmicosin gelatin microcapsule in rats were operated to control the quality of the preparation process and provide pharmacokinetic parameters for clinical use,the results showed that :?1?There were no significant differences in yield,entrapment efficiency,drug loading quantity,burst release rate and particle size between the medicinal grade B skin gelatin group and the medicinal grade B bone gelatin group?P > 0.05?;the yield of 0.2%Tween80 group was significantly higher than that of 0.3% Tween80 group?P < 0.01?,and there was no significant difference between 0.1% Tween80 group and 0.1% Tween80 group?P > 0.05?,the entrapment efficiency and drug loading quantity of 0.2% Tween80 group were significantly higher than both 0.1% Tween80 group and 0.3% Tween80 group?P < 0.01?,and the burst release rate of 0.2% Tween80 group and 0.3% Tween80 group was significantly lower than that of 0.1% Tween80 group?P < 0.01?.Compared with reagent-grade excipients group?P < 0.01?,there was no significant difference in other indicators?P>0.05?,and there was no significant difference in the size of microcapsules among groups?P > 0.05?.Indicate that both medical grade B-type skin gelatin and B-type bone gelatin can be used to prepare telmicosin gelatin microcapsules.The yield,encapsulation efficiency,drug loading quantity,bitterness grade and particle size of telmicosin gelatin microcapsules prepared by single coagulation of pharmaceutical grade B-type skin gelatin,Tween-80,glutaraldehyde and anhydrous sodium sulfate were 71.33%,79.33%,22.16%,1 and 41.46 ?m respectively.?2?The total content of SO₄^2--in tilmicosin gelatin microcapsules was 4.89 ±0.07%,which was lower than that of the listed drugs?heparin?;the content of glutaraldehyde in tilmicosin gelatin microcapsules was 0.02±0.01% and less than 0.5%.Indicate that the contents of total sulfate ion and glutaraldehyde in tilmicosin gelatin microcapsules were compliance with the requirements.?3?Tilmicosin gelatin microcapsules were given orally to rats at a dose of 36 mg/kg,compared with tilmicosin powder,the Tmax,t_1/2 and AUC of tilmicosin gelatin microcapsules were increased by 116.3%,564.13%,273.23%,and the relative bioavailability was 3.7 times higher.The Tmax,t_1/2 and AUC were 96.16%,514.69% and 254.96% higher than that of the powder when the rats were given a single oral dose of 72mg/kg tilmicosin gelatin microcapsules,and the relative bioavailability was 3.7 times higher than that of the powder.Compared with tilmicocin powder,timicosin gelatin microcapsules increased by 88.89%,125.64%,154.94% and 63.37% in Tmax,t_1/2,AUC and steady-state blood trough concentration,decreased by 53.18% in volatility and 2.5 times in relative bioavailability,when temicocin gelatin microcapsules were orally administered to rats at 72 mg/kg for several times.Indicate that tilmicosin gelatin microcapsules had a sustained release effect,improved the bioavailability of the powder,and no burst release was observed.