注射用醋酸奥曲肽微球体内外释放度分析

Study for the analysis of the in vivo and in vitro release of octreotide acetate microspheres for injection

目的:研究注射用醋酸奥曲肽微球体外释放度加速试验方法,并探讨与体内释放的相关性,为该制剂的有效性评价研究提供参考。方法:分别采用转瓶法和流池法考察了温度、pH、转速、流速、样品池的种类、膜的排列方式、玻璃珠以及加样方式等影响因素,建立了体外加速释放在温度37℃、片剂池(22.6 mm)、流速16 mL·min-1和pH 10.0缓冲液中进行的流池法,并与在温度37℃、转速6 r·min-1和pH 10.0缓冲液中进行的转瓶法进行对比。结果:注射用醋酸奥曲肽微球在流池法中的释放均快于转瓶法中的释放;且2种制剂样品不同方法测定结果趋势一致,制剂A释放快于制剂B;对流池法体外加速释放-体内释放进行线性回归,制剂A和B相关系数r分别为0.998 2、0.960 9。结论:采用流池法测定的体外加速释放快于转瓶法,且与体内释放具有良好的相关性(r>0.9),为评价奥曲肽微球制剂的体内外释放提供参考。

Objective:To study the method of accelerated release of octreotide acetate microspheres for injection in vitro,and to establish the correlation between in vivo and in vitro.Methods:The rotating-bottle method and the flow-through cell method were established.Rotational speed,flow velocity,temperature,pH value,sample pool of species,the arrangement of membrane,glass bead and influence factors such as the way for the accelerated release in vitro was investigated,and the flow-through cell methodwith the temperature of 37℃,tablet cell(22.6 mm),speed 16 mL·min-1 and pH 10.0 buffer,and the rotating-bottle method with the temperature of 37℃,of 6 r·min-1 and pH 10.0 bufferwas compared.The concentration of octreotide in rat plasma was determined by LC-MS method.Results:The release rates of octreotide acetate microspheres for injection with the flow-through cell method were faster than that with the rotating-bottle method.The results of the two methods showed the same trend,indicating that the release of brand A was faster than that of brand B.The correlation coefficient r form the linear regression analysis of the correlation between in vitro accelerated release and in vivo release by the flow-through cell method was 0.9982 and 0.9609 for brand A and brand B,respectively.Conclusion:The accelerated in vitro release measured with the flow-through cell method is faster than that by the rotating-bottle method,and has a good correlation with the in vivo release(r>0.9).The method could be a reference for the evaluation of the in vivo and in vitro release of octreotide acetate microspheres for injection.