超临界二氧化碳流体制备拉帕替尼固体分散体的考察

Investigation of supercritical CO_2 fluid technology in preparation of solid dispersions of lapatinib

目的采用超临界二氧化碳(CO_2)流体制备拉帕替尼固体分散体,提高拉帕替尼的体外溶出度。方法考察载体种类、药载比、工艺条件(压力、温度、制备时间)对固体分散体中拉帕替尼溶出情况的影响,筛选制备工艺。结果工艺条件为45℃、20 MPa、2 h时,药载量为35%的拉帕替尼-Soluplus固体分散体的溶出速率较原料药显著提高,在p H=1.0介质中90 min溶出率约97%。由差示扫描量热法和粉末X射线衍射法分析可知,拉帕替尼以无定形状态和微晶态分散于载体中。结论采用超临界CO_2法制备的拉帕替尼-Soluplus固体分散体的体外溶出度较拉帕替尼原料药明显提高,工艺简单,为其工业化生产提供了基础。

Objective The solid dispersions(SDs)of Lapatinib were prepared by supercritical CO2fluids technology to improve the in vitro dissolution.Methods The effects of carrier type,weight ratio of drug to carrier,temperature and pressure of supercritical CO2and reaction time on the dissolution profiles of Lapatinib from the SDs were investigated to screen the preparation process.Results The rate and extent of dissolution of Lapatinib from the optimal SDs with soluplus as carriers and drug-to-carrier ratio of35%prepared at45℃and20MPa for2h were significantly increased compared with the bulk drug.The dissolution of Lapatinib in pH=1.0medium at90min from the optimal SDs was about97%.The results of differential scanning calorimetry and powder X-ray diffractometry showed that Lapatinib existed in amorphous and microcrystal state in carriers in SDs.Conclusions Using soluplus as the carrier,the solid dispersion prepared by supercritical CO2method can obviously improve the dissolution rate of Lapatinib in vitro,which provides the basis for industrial production.