三维有序大孔壳聚糖／尼莫地平固体分散体的研究

Dissolution, Stability and Pharmacokinetics of Solid Dispersions Made from Three Dimensionally Ordered Macroporous Chitosan Matrix and Nimodipine

目的制备孔径为470nm的三雏有序大孔壳聚糖／尼莫地平的固体分散体，研究其释药特点、稳定性和药动学。方法利用溶剂蒸发法制备固体分散体，通过药物释放试验考察固体分散体在模拟胃肠液介质中的释放行为；通过含量测定、X-射线衍射和溶出试验检查固体分散体的稳定性；大鼠分别给予自制固体分散体和市售片粉末，测定血药浓度。结果固体分散体在pH6.8的介质中的溶出度明显比pH1.2和pH4.5介质中高，在梯度pH介质中的释药曲线类似阶梯型；结晶度和溶出度在考察时间内基本无变化；自制固体分散体的AUC0.12h是市售制剂的1.91倍，具有长效作用。结论自制固体分散体稳定性良好，能够提高尼莫地平的大鼠口服生物利用度。

OBJECTIVE To prepare solid dispersions containing chitosan matrix with three dimensionally ordered 470 nm macroporous and nimodipine （3D-CS/NMDP）, investigate the drug release, stability and pharmacokinetics. METHODS The solid dispersions were prepared by solvent evaporating method. The drug release behaviors of the 3D-CS/NMDP solid dispersions in artificial gastrointestinal fluid were examined by dissolution experiments. The chemical, crystal and dissolution stability was determined by X-ray diffraction method and dissolution method respectively. After orally administrating the 3D-CS/NMDP solid dispersions and commercial preparations, the plasma drug concentration of rat was measured. RESULTS The dissolution of the solid dispersion in pH 6.8 medium was largely higher than that in pH 1.2 and pH 4.5 medium. Drug release curve in gradient pH media expressed Ladder type. The crystallinity and dissolution of the solid dispersion hardly changed in test period. The 3D-CS/NMDP solid dispersions had 1.91 times AUC0-12 h of commercial preparations, and possessed prolonged action. CONCLUSION The self-made 3D-CS/NMDP solid dispersions have good stability, can markedly improve the bioavailability in rat after oral administration.