阿苯达唑纳米晶体的制备与表征

目的： 采用微射流高压均质-喷雾干燥法技术制备阿苯达唑纳米晶体，并进行表征和体外溶出考察。方法： 釆用高压均质法制备阿苯达唑纳米混悬液，并进一步喷雾干燥得纳米晶体。通过正交试验优化制备工艺；对最佳制备工艺所得纳米晶体进行粒径测定、DSC分析和傅里叶红外图谱分析，并测定其体外溶出度。结果： 微射流高压均质最佳制备工艺条件：在均质温度35℃，103.44 MPa和137.93 MPa下各循环20次，得到纳米混悬液平均粒径为（363.52±1.5） nm。喷雾干燥最佳工艺为：进样速度5 mL·min^-1，进风温度180℃，在此条件下得粉率（66.71±0.96）%，含水量（6.61±0.16）%，平均粒径367.34±0.68 nm。DSC分析及傅里叶红外图谱结果表明制备成纳米晶体后形成新的物象；体外溶出度实验结果表明，纳米晶体的溶出度显著高于原料药和混合物。结论： 微射流高压均质-喷雾干燥工艺，可以制备平均粒径小且较为均匀的纳米晶体；纳米化后形成新的物象，可以明显提高阿苯达唑的溶出性能，利于改善药物的口服吸收，这为阿苯达唑进一步开发提供了依据。

Preparation and characterization of albendazole nanocrystals

OBJECTIVE To prepare albendazole nanocrystals by micro-jet high-pressure homogenization-spray drying technique, and to characterize and investigate the dissolution in vitro. METHODS Albendazole nanosuspension was prepared by high pressure homogenization and further spray-dried.The preparation process was optimized by orthogonal test; the nanocrystals obtained by the best preparation process were subjected to particle size determination, DSC analysis and Fourier infrared spectroscopy analysis, and their in vitro dissolution was determined. RESULTS The optimal preparation conditions of micro-jet high-pressure homogenization were as follows:20 cycles of homogenization temperature of 35℃, 103.44 MPa and 137.93 MPa, and the average particle size of the nano-suspension was (363.52±1.5) nm. The optimal spray drying process was as follows:injection speed 5 mL·min^-1, inlet air temperature 180℃, under this condition, the powder yield is (66.71±0.96)%, the water content is (6.61±0.16)%, and the average particle size is (367.34±0.68) nm. The results of DSC and Fourier transform infrared(FTIR) analysis showed that the nanocrystals formed new substance after preparation, and the dissolution test in vitro showed that the dissolution rate of nanocrystals was significantly higher than that of drug substance and mixture. CONCLUSION The micro-jet high-pressure homogenization-spray drying process can prepare nanocrystals with small and uniform size. The formation of new substance after nanocrystallization can significantly improve the dissolution properties of albendazole and improve the oral absorption of the drug, which provides a basis for the further development of albendazole.