Box-Behnken效应面法优化塞来昔布微粉化工艺

Box-Behnken Experimental Design to Optimize Micromization Process of Celecoxib by Air Jet Mill

关键词:  气流粉碎  塞来昔布  粉碎压力  进料压力  Box-Behnken效应面法

Key words:  air jet mill  celecoxib  grinding pressure  pushing pressure  Box-Behnken experimental design

摘要:

目的 采用气流粉碎技术进行塞来昔布微粉化试验研究，并对其体外溶出度进行考察。方法 通过对微粉化工艺参数优化，以粉碎压力(X₁，psi)、进料压力(X₂，psi)为考察对象，以D50(Y₁，μm)、D90(Y₂，μm)为评价指标，利用Box-Behnken效应面法优化微粉化工艺参数，采用Malvern粒度仪测定微粉化塞来昔布的粒径分布，扫描电镜考察其形态；并比较微粉化塞来昔布、参比制剂(西乐葆)和原料药的溶出速率和溶出量。结果 微粉化塞来昔布粒径D₅₀为1.07 μm，D90为3.71 μm，扫描电镜显示微乳粒径均一，制备的微粉化塞来昔布的体外累积溶出度明显高于原料药。结论 塞来昔布微粉化工艺采用Box-Behnken实验设计法优化简单、可行。

Abstract:

OBJECTIVE To study on the micromization process of celecoxib which was carried on with an air jet mill, and to investigate its in vitro drug dissolution behavior. METHODS The micromization process parameters were optimized by Box-Behnken Design of response surface methodology (RSM) of grinding pressure(X₁, psi), pushing pressure (X₂, psi) as independent variables and particale size D50(Y₁, μm), D90(Y₂, μm) as dependent variables. The optimized micromization celecoxib was characterized for particle size and morphology. The dissolution rate and the dissolution amount of micromization celecoxib, reference formulation, and API were determined and compared. RESULTS Particle size of micromization celecoxib was found to be D₅₀ 1.07 μm, D90 3.71 μm. And the micromization celecoxib was found to be small and homogeneous as seen in scan electron microscopy. The in vitro accumulated dissolution of micromization celecoxib was higher than that of the API. CONCLUSION The Box-Behnken experimental design used to optimize micromization process of celecoxib by air jet mill was simple and practical.