微型化介质研磨法制备难溶性黄酮类化合物纳米混悬剂

目的探讨微型化介质研磨法制备难溶性黄酮类化合物纳米混悬剂(NS)的可行性。方法以磁力搅拌器为动力装置,西林瓶为研磨室,采用氧化锆珠子为研磨介质构建微型化介质研磨法制备槲皮素(QCT)、黄芩苷(BCN)、葛根素(PRN)及水飞蓟素(SLR)4种黄酮类化合物NS,以平均粒径、多分散度指数(PDI)和稳定性指数(SI)为指标,对工艺参数转速、研磨介质用量和研磨时间进行优化。结果 QCT-NS、BCN-NS、PRN-NS和SLR-NS制备的最佳工艺参数转速、研磨时间、氧化锆用量与药物混悬液比例分别为QCT-NS 800 r/min、8 h、1∶1,BCN-NS 800 r/min、24 h、1∶1,PRN-NS800 r/min、24 h、2∶1,SLR-NS 800 r/min、12 h、1∶1;以最佳工艺参数制备所得QCT-NS、BCN-NS、PRN-NS和SLR-NS的平均粒径均在400 nm以下,QCT-NS、BCN-NS和SLR-NS的PDI在0.3以下,SI高于0.75;PRN-NS的PDI和SI分别为0.41和0。结论微型化介质研磨法制备难溶性黄酮类化合物NS工艺简单、稳定可行,值得进一步深入研究。

Preparation of insoluble flavonoids nanosuspensions by miniaturized media milling

Objective To study the feasibility of preparing insoluble flavonoids nanosuspensions (NS) by miniaturized media milling. Methods The miniaturized media milling method was constructed with the magnetic stirrer, vial and zirconia beads as the power plant, milling chamber and milling media to prepare the nanosuspensions of four flavonoids:quercetin (QCT), baicalin (BCN), puerarin (PRN), and silymarin (SLR). The process of stirring speed, the amount of milling medium and the milling time were optimized with average particle size, polydispersity index (PDI) and stability index (SI) as indicators. Results The optimized process of stirring speed, the amount of milling medium and the milling time of QCT-NS, BCN-NS, PRN-NS and SLR-NS were QCT-NS 800 r/min, 8 h, 1:1, BCN-NS 800 r/min, 24 h, 1:1, PRN-NS 800 r/min, 24 h, 2:1, SLR-NS 800 r/min, 12 h, 1:1. The average particle sizes of QCT-NS, BCN-NS, PRN-NS and SLR-NS prepared with the optimized process were below 400 nm. The PDI of QCT-NS, BCN-NS and SLR-NS was below 0.3 (PRN-NS) and SI was above 0.75, the PDI and SI of PRN-NS were 0.41 and 0, respectively. Conclusion The miniaturized media milling methods for preparation of insoluble flavonoids NS is simple, stable and feasible, and it is worth for further study.