超临界CO₂制备尼莫地平固体分散体的研究

【作者】 岑琴；

【导师】 周丽莉；

【作者基本信息】 沈阳药科大学 ， 生物化工， 2008， 硕士

【摘要】 本研究采用超临界CO₂法制备尼莫地平固体分散体,以期改善水难溶性药物尼莫地平的溶出速率,提高其生物利用度。采用高效液相法（HPLC）测定尼莫地平在不同介质中的溶解度,紫外分光光度法测定尼莫地平固体分散体中药物的含量和体外溶出度。方法学考察结果表明这些分析方法线性关系良好,回收率较高,日内、日间精密度的相对标准偏差（RSD）均低于2%,方法准确可靠。以尼莫地平的体外溶出度为指标,在单因素实验考察的基础上,采用正交实验优化超临界CO₂法制备尼莫地平固体分散体的工艺条件。根据实验结果确定了超临界CO₂法制备尼莫地平固体分散体的优化工艺条件为:聚乙烯吡咯烷酮（PVPK30）为载体材料,尼莫地平与PVPK30的比例1:8,超临界CO₂制备温度55℃,压力25MPa,时间7h。将制备所得的固体分散体进行体外溶出度实验,药物在60min的累积溶出率为97.66%,显著高于溶剂法制备所得固体分散体在60min的累积溶出率74.67%。差示扫描量热实验（DSC）表明药物以无定型或分子状态存在于固体分散体中:而溶剂法制备所得的固体分散体中,部分ND与PVPK30形成玻璃态固熔体,部分ND依旧以晶体形态存在。将优化工艺条件制备所得的固体分散体直接装胶囊,制备尼莫地平速释胶囊,并将自制的速释胶囊与市售的普通片剂进行体外溶出度实验。实验结果表明,自制的尼莫地平速释胶囊在30min的累积溶出率为93.12%,优于市售尼莫地平普通片剂在30min的累积溶出率70.61%。更多还原

【Abstract】 Nimodipine solid dispersion was prepared by supercritical CO₂ method to improve the dissolution and bioavailability of nimodipine that is poorly water soluble.Methods of content assay and in-vitro release test （UV spectrophotography） and relative substances detection （HPLC） were respectively carried out. All methods had good linearity, sufficient recovery and good accuracy. The RSD of intraday and interday precision are lower than 2%Using dissolution in vitro of nimodipine as index, orthogonal experiment was done based on single factor experiments and the optimal conditions were: PVPK30 was the carrier material, the proportion of nimodipine and PVPK30 was 1:8, supercritical experiment time was 7h, temperature 55℃, pressure 25MPa. Dissolution in vitro of solid dispersion prepared indicated that accumulating dissolution in 60min was 97.66% and 74.67% prepared by solvent evaporation method. Nimodipine was in amorphous phase or dispersed in molecules, indicated by differential scanning calorimeter （DSC）.The solid dispersion prepared in optimal condition was encapsulated and fast release capsule was obtained. Dissolution in vitro of the capsule and nimodipine tablet saled showed that dissolution rate of the capsule was 93.12%, better than tablet saled which dissolution rate was 70.61%.更多还原