热熔挤出法和喷雾干燥法制备布洛芬固体分散体的比较

The comparison of solid dispersions of ibuprofen prepared by hot melt extrusion method and spray drying method

目的比较热熔挤出法和喷雾干燥法制备的布洛芬固体分散体的溶解度、体外溶出速度及药物存在状态方面的差异。方法以聚乙烯吡咯烷酮(PVP K30)为载体,药物载体质量比例为1∶3,通过热熔挤出法和喷雾干燥法制备布洛芬的固体分散体,测定并比较它们在0.1 mol·L-1盐酸中的溶出差异;采用差示扫描量热分析实验(differential scanning calorimetry,DSC)和X射线衍射实验(X-ray diffractometer,XRD)对布洛芬固体分散体进行物相鉴别。结果与布洛芬原料药和物理混合物相比,热熔挤出工艺对药物的溶解度和溶出度提高较明显,喷雾干燥工艺对药物的溶解度和溶出度提高非常显著;物相鉴别表明,物理混合物中药物仍有部分以晶体形式存在,采用热熔挤出和喷雾干燥工艺制备的固体分散体中药物均以无定形状态存在。结论相比热熔挤出法,采用喷雾干燥法制备的布洛芬-PVP K30固体分散体更能显著提高药物的溶解度和溶出度,布洛芬在30 min内即可接近完全释放。

Objective To compare the differences of saturated solubility, dissolution and phase state of ibuprofen solid dispersions prepared by hot melt extrusion method and spray drying method. Methods Using polyvinyl pyrrolidone(PVP K30) as carrier, with drug to carrier ratio of 1∶3, ibuprofen solid dispersion was prepared by hot melt extrusion(HME) and spray drying(SD) method, and the saturated solubility and dissolution of ibuprofen solid dispersion in 0.1 mol·L-1HCl were determined and compared. Differential scanning calorimetry(DSC) and X-ray diffractometer(XRD) were used to investigate the ibuprofen status in the solid dispersions. Results The saturated solubility and dissolution of ibuprofen were obviously and significantly increased by HME and SD method compared with ibuprofen raw material and its physical mixture. Phase identification showed that part of ibuprofen in physical mixture still exists in crystal form, however, ibuprofen exist in amorphous state in solid dispersions prepared by HME&SD methods. Conclusion Compared with hot melt extrusion method, ibuprofen–PVP K30 solid dispersion prepared by spray drying method can significantly improve the saturated solubility and in vitro dissolution of ibuprofen, and ibuprofen can achieve complete release within 30 min.