不同工艺制备的替米考星颗粒体外释放度研究

Study on in Vitro Dissolution of Tilmicosin Granules with Different Preparation Processes

通过考察3种替米考星颗粒制剂在酸性溶液和缓冲液中的释放情况,为新制剂的进一步研发和临床应用提供理论依据。采用高效液相色谱法对3种不同制剂中替米考星的含量及其体外溶出度进行测定。色谱柱选择Hypersil ODS-2 C18(4.6 mm×250 mm,5μm),以水∶乙腈∶四氢呋喃∶磷酸二丁胺(790∶130∶55∶25)为流动相,流速1.0 mL/min,检测波长290 nm,柱温30℃。分别以盐酸溶液和磷酸盐缓冲液为溶出介质,测定3种新研制的替米考星不同制剂体外溶出曲线,溶出方法选用浆法,转速为75 r/min,温度为37℃±0.5℃。在所建立的方法学基础上,替米考星在10μg/mL~1000μg/mL范围内与峰面积呈良好的线性关系,在90 min时3种新研制的替米考星不同制剂在酸性溶液中的溶出度分别为100%、5.73%和8.29%,供试品1与供试品2、供试品3及对照品之间差异显著(P<0.05),供试品2、供试品3与对照品之间无明显差异;120 min时3种新研制的替米考星不同制剂在磷酸盐缓冲液中的累积溶出度分别为100%、97.53%和93.60%,3种供试品与对照品差异不显著(P>0.05)。3种不同工艺制备的替米考星颗粒,在酸性溶液和磷酸盐缓冲溶液中累积溶出度差异显著(P<0.05),根据不同的给药途径选择不同的制剂,具有良好的临床应用效果。

By investigating the dissolution of three tilmicosin granule preparations in acidic solutions and phosphate buffers,a reliable theoretical basis for the further development and clinical application of new preparations is provided.The contents and in vitro dissolutions of tilmicosin in three different formulations were determined by high performance liquid chromatography.The chromatographic column is Hypersil ODS-2 C18(4.6 mm×250 mm,5μm),with water∶acetonitrile∶tetrahydrofuran∶dibutylamine phosphate(790∶130∶55∶25)as mobile phase,flow rate 1.0 mL/min,the wavelength 290 nm,and the column temperature 30℃.Using hydrochloric acid solution and phosphate buffer as dissolution medium,the in vitro dissolution curves of three newly developed different preparations of tilmicosin were determined.The dissolution method was slurry method,the rotating speed was 75 r/min,and the temperature was 37℃±0.5℃.Based on the established methodology,tilmicosin showed a good linear relationship with the peak area in the range of 10μg/mL-1000μg/mL.At 90 min,the cumulative dissolution rates of three newly developed tilmicosin formulations in acid solution were 100%,5.73%,and 8.29%,respectively.There was significant between test article 1,test article 2,test article 3,and reference substance(P<0.05),and there was no significant difference between test article 2 and test article 3;At 120 min,the cumulative dissolution rates of three newly developed tilmicosin preparations in phosphate buffer were 100%,97.53%,and 93.60%,respectively,and there was no significant difference among the three test products and the reference product(P>0.05).The cumulative dissolutions of tilmicosin granules prepared by three different processes were significantly different in acidic solution and phosphate buffer solution(P<0.05).Different preparations were selected according to different administration routes,which should have good clinical application effect.