尼群地平固体分散体微丸的制备与评价

Preparation and Evaluation of Nitrendipine Solid Dispersion Pellets

目的采用小型离心造粒技术制备尼群地平固体分散体微丸。方法以微丸的粉体学性质、收率(Yield)和10min药物累积溶出量(P10)为评价标准,通过处方单因素试验考察可溶性载体、不溶性载体及两者的比例对微丸质量的影响;通过制备工艺单因素试验,考察润湿剂中乙醇的浓度及用量、离心造粒转速及时间对微丸质量的影响;并通过X射线粉末衍射(XRD)和差示扫描量热法(DSC)试验对药物的可能存在状态进行判断。结果尼群地平固体分散体微丸的处方与制备工艺为:可溶性载体采用泊洛沙姆(F68),不溶性载体采用低取代羟丙基纤维素(L-HPC),两者的比例为2:7,润湿剂为70%乙醇,用量25ml,离心造粒转速为300r/min,时间30min,所得微丸P10达86%以上。XRD和DSC实验表明,药物以无定形存在于固体分散体中,但在微丸中有少量晶体析出。结论采用上述方法制备的尼群地平固体分散体微丸,具有固体分散体结构和显著的速释特征。

Objective To prepare nitrendipine solid dispersion pellets by centrifugal granulation technology. Methods Take micromeritieal properties,yield percentage and drug dissolution rate of pellets as main index, formulation factors of varieties and content of soluble and insoluble carriers, and technology factors such as quantity and ethanol concentration of the wetting agent, centrifugal speed and time were investigated by means of the influence factors test. Physical states of drug in pellets were characterized using X ray diffraction analysis（XRD） and differential scanning calorimetry（DSC）. Results Using 70% ethanol as the wetting agent, pellets composing of nitrendipine （10%）, poloxamer F68 （20%） and low-substituted hydroxypropylcellulose（70%） prepared at a centrifugal speed of 300 r/min for 30 min were more preferable than others, and percentage of drug dissolved in which in the first 10 min was more than 86%. XRD and DSC tests showed the presence of diffraction peaks in pellets and absence in solid dispersion, which suggested that amorphous nitrendipne in solid dispersion was crystallized in the process of pellets preparation. Conclusion Nitrendipine solid dispersion pellets prepared by centrifugal granulation technology has a structure of solid dispersion and property of immediate-releasing.