流通池法在泊沙康唑口服混悬液体外溶出研究中的应用

Application of flow-through cell apparatus in the in vitro dissolution of posaconazole oral suspension

目的建立一种有区分力的流通池法检查泊沙康唑口服混悬液的体外溶出。方法以研磨法制成不同粒度分布的泊沙康唑混悬液中间体,并通过调节辅料黄原胶的加入量,制备成具有不同粒度分布和不同黏度的泊沙康唑口服混悬液。对关键参数(玻璃珠用量、加样方式以及流速)进行筛选,建立检查泊沙康唑口服混悬液体外溶出的流通池法。用新建立的流通池法和FDA溶出度数据库收载的桨法分别检测泊沙康唑口服混悬液的体外溶出曲线。结果桨法测得的溶出曲线药物释放较快,20 min时已基本释放完全;而新建立的流通池法测得的溶出曲线药物释放缓慢,并且对混悬液的粒度分布和黏度差异显示出良好的区分力。结论与桨法相比,流通池法检查泊沙康唑口服混悬液的体外溶出时具有更高的区分力。

Objective To establish flow-through cell apparatus to test the in vitro dissolution of posaconazole oral suspension with good discrimination.Methods Posaconazole suspension intermediates with different particle sizes were prepared by bead-milling method.Posaconazole oral suspensions with different particle sizes and viscosities were prepared by adjusting the amount of addition in excipient xanthan gum.The flow-through cell apparatus for testing the dissolution of posaconazole oral suspension was established by screening the key parameters:the amount of glass beads,the way of adding samples and the flow rate.The in vitro dissolution profiles of the posaconazole oral suspensions were tested by the newly constructed flow-through cell apparatus and the paddle apparatus recorded in the FDA dissolution methods database.Results The dissolution profiles measured by the paddle apparatus showed faster release of the drug,and the drug was released at most completely at 20 min;while the newly established flow-through cell apparatus demonstrated slow release,with good discrimination for the particle size and viscosity of the suspension.Conclusion Compared with the paddle apparatus,the flow-through cell apparatus has better discrimination for the in vitro dissolution of posaconazole oral suspension.