苯妥英固体分散体3种制备方法比较

Comparison of Three Preparation Methods of Phenytoin Solid Dispersion

目的比较3种方法制备的苯妥英固体分散体(SD)的理化性质。方法以高熔点(296℃)难溶性药物苯妥英原料药(API)为模型药,分别采用喷雾干燥技术、热熔挤出技术、共喷共挤(喷雾干燥结合热熔挤出)技术制备苯妥英SD。选择X射线粉末衍射(XRPD)、差示扫描量热(DSC)法,进行溶出度、表观溶解度、稳定性试验,分析不同方法制备的SD的物相状态、溶出性能和稳定性。结果XRPD和DSC分析结果显示,喷雾干燥技术和共喷共挤技术可制备无定形态SD,以热熔挤出技术制备时存在少量微晶;热台显微镜观察结果显示,共喷共挤技术制备的SD相容性较好;溶出度和表观溶解度试验结果显示,3种SD的溶出度和溶解度均较好;稳定性试验结果表明,共喷共挤技术制备的SD稳定性较好。结论3种方法制备的SD溶出性能均较好;其中共喷共挤技术制备的SD稳定性更好,该技术对于提升高熔点难溶性药物的溶出性能和稳定性具有借鉴意义。

Objective To compare the physicochemical properties of phenytoin solid dispersions prepared by three methods.Methods The phenytoin solid dispersions were prepared by spray drying technology,hot melt extrusion technology and co-spray coextrusion(spray drying combined with hot melt extrusion)with phenytoin active pharmaceutical ingredients[a drug with a high melting point(296℃)and slightly solubility]as model drug.X-ray powder diffraction(XRPD)and differential scanning calorimetry(DSC)and the dissolution,apparent solubility and stability tests were selected to analyze the physical state,dissolution performance and stability of solid dispersions which prepared by different methods.Results The results of XRPD and DSC tests showed that amorphous solid dispersions could be prepared by spray drying technology and co-spray coextrusion technology,but the solid dispersions prepared by hot melt extrusion technology had small microcrystalline.The results of hot stage microscope test showed that solid dispersions prepared by co-spray coextrusion technology had good compatibility.The results of dissolution and apparent solubility tests showed that solid dispersions prepared by these three methods had good dissolution and solubility.The stability test results showed that solid dispersions prepared by co-spray coextrusion technology had good stability.Conclusion The dissolution performance of solid dispersions prepared by the three methods was good,and the stability of solid dispersions prepared by co-spray coextrusion technology was better.The co-spray coextrusion technology has reference significance for improving the dissolution performance and stability of insoluble drugs with high melting points.