Study On Quality Evaluation And Pharmacodynamics Of Tilmicosin Gelatin Microspheres

Tilmicosin belongs to a macrolides broad-spectrum antibiotic.In our laboratory,tilmicosin gelatin microcapsules were prepared using a simple coacervation method by taking type B gelatin as a capsule material and tilmicosin as a core material.To determine a content measurement method of tilmicosin gelatin microcapsules,in-vitro dissolution characteristics,drug stability and characteristics of metabolism in an animal body,by establishment and verification of the content measurement method of tilmicosin gelatin microcapsules,measurement of the in-vitro release rate,the stability test of tilmicosin gelatin microcapsules,the non-clinical pharmacokinetics test of tilmicosin gelatin microspheres and the stability test of microcapsules in rumens,an ultraviolet spectrophotometry(UV)and a high performance liquid chromatography(HPLC)which are used for measuring the content of tilmicosin gelatin microcapsules were established;drug release rates of microcapsules in an acid and a buffer solution were measured;the influence of high temperature,high humidity and intense light irradiation on the stability of microcapsules was investigated and the stability thereof was measured,to determine the preservation time duration of tilmicosin gelatin microcapsules;by taking a pig as a target animal,a study on non-clinical target animal pharmacokinetics of tilmicosin gelatin microspheres in the body of the target animal was conducted;and the stability of microcapsules was detected in a ruminant rumen using a nylon bag technique.The results showed that:(1)The specificity?good linearity(R2UV=0.9994;R2HPLC=0.9995)?accuracy(recovery rates were all within the range of 98%-102%,RSD<2%)and precision(RSD<2%)of the established UV(determining at a wavelength of 291nm)and HPLC(C18 column:5?m,4.6mm×250mm;flow rate:1.0mL/min;taking water-acetonitrile-DPAP-tetrahydrofuran as a mobile phase;wavelength:280nm)which were used for determining the content of tilmicosin gelatin microcapsule all conform to the provisions,indicating that the UV and HPLC meet the requirements of measuring the content of tilmicosin gelatin microcapsules.(2)The release rate(7.38%)of tilmicosin gelatin microcapsules in the acid solution for 2h was less than 10%,the final release rate(98.08%)in the buffer solution was greater than 90%,and the release rate of tilmicosin original powder for 2h was 87%,indicating that tilmicosin gelatin microcapsules conform to criteria of enteric-coated preparations,and have obvious sustained-release effects in vitro.(3)For the tilmicosin gelatin microcapsules in bright light for 0-10d,the microcapsule color was changed into faint yellow from brown yellow and the drug content of microcapsules was reduced by 11.29%>5%;the drug content thereof on the tenth day at high temperature of 60 ? is reduced by 8.52%>5%,indicating that microcapsules was instable in bright light and at high temperature;and it was calculated according to reaction kinetics that the preservation time durations of tilmicosin gelatin microcapsules at room temperature in an acceleration condition and a long-term test condition were 1.93 years and 1.79 years respectively.(4)It was found from the pharmacokinetics study that a tilmicosin gelatin microcapsule pharmacokinetics model belongs to a one-compartment open model,the main pharmacokinetics parameters thereof:elimination phase half-life,area under concentration-time curve,peaking time and bioavailability was respectively increased by 410.64%?163.86%?150.00%and 30.85%as compared with those of the tilmicosin original powder,thereby indicating that tilmicosin gelatin microcapsules have the advantages of slow elimination of oral administration,long peaking time and high bioavailability and can have sustained-release long-acting effects.(5)The degradation rate of tilmicosin gelatin microcapsule was gradually increased with the prolongation of stay time duration thereof in a bovine rumen,and the degradation rate of 24h reaches 60%,indicating that the stability of tilmicosin gelatin microcapsules in the bovine rumen was poor,thereby not being suitable for ruminant.