基于阿拉伯半乳糖的白藜芦醇固体分散体制备及体外评价

Preparation and in Vitro Evaluation of Solid Dispersion of Resveratrol Based on Arabinogalactan

目的研究阿拉伯半乳糖(AG)作为一种新型多糖类载体在固体分散体制剂中的应用,选用难溶性的白藜芦醇(RES)为模型药物,制备白藜芦醇-阿拉伯半乳糖固体分散体(RES-AG SD)并进行评价。方法以AG为载体,采用溶剂法制备RES-AG SD,运用差示扫描量热法(DSC)、X射线粉末衍射法(XRPD)、傅里叶变换红外光谱(FTIR)和电子扫描显微镜(SEM)分析方法对其微观结构进行表征和分析,选用浆法研究原料药及RES-AG SD在pH 1.2盐酸溶液及pH 6.8磷酸盐缓冲液中的溶出情况;并对其初步稳定性进行评价。结果SEM观察发现RES-AG SD呈细碎的不规则颗粒状,RES和AG的形貌特征已不见;DSC、XRPD和FTIR结果显示,RES晶型被破坏,晶体衍射峰基本消失,药物以无定形形态分散于载体AG中,药物与载体之间存在一定的相互作用;体外溶出实验表明,2 h时,RES在2种溶出介质中的累计溶出率皆高达90%以上,与原料药相比溶出度得到显著提高;30 d加速稳定性实验结果显示,RES-AG SD溶出度与0月相比未发生明显改变,表明其能够保持一定的稳定性。结论所制备的RES-AG SD能显著改善RES的溶出度,为RES的有效递送提供了新的制剂类型;AG作为一种新型药用功能性固体分散体载体,具有一定的实际应用价值。

OBJECTIVE To study the application of arabinogalactan(AG)as a new type of polysaccharide carrier in solid dispersion formulations,select insoluble resveratrol(RES)as the model drug to prepare resveratrol-arabinogalactan solid dispersion(RES-AG SD)and evaluate it.METHODS RES-AG SD was prepared by solvent method with AG as carrier.Its microstructure was characterized and analyzed by differential scanning calorimetry(DSC),X-ray powder diffraction(XRPD),Fourier transform infrared spectroscopy(FTIR)and scanning electron microscopy(SEM).The dissolution of API and RES-AG SD in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution was studied by slurry method,and their preliminary stability was evaluated.RESULTS SEM observation showed that RES-AG SD was in the shape of fine irregular particles,and the morphology of RES and AG was not seen.The results of DSC,XRD and FTIR showed that the crystal form of RES was destroyed and the diffraction peak of RES was almost disappeared.The drug was dispersed in AG in amorphous form,and there was a certain interaction between drug and carrier.In vitro dissolution experiments showed that the cumulative dissolution rate of RES in the two dissolution media was more than 90%at 2 h,and the dissolution rate was significantly improved compared with that of API.The results of 30 d accelerated stability test showed that the dissolution rate of RES-AG SD did not change significantly compared with that in 0 month,indicating that RES-AG SD could maintain a certain stability.CONCLUSION The prepared RES-AG SD can significantly improve the dissolution of RES,which provides a new route for the effective delivery of RES.As a new carrier of functional solid dispersion,AG has a certain practical application value.