微通道反应器制备白藜芦醇纳米分散体

Formation of poorly water-soluble oral drug nanodispersions in a microchannel

对微通道反溶剂沉淀法制备白藜芦醇(RES)纳米药物分散体进行了研究。采用T型微通道反应器优化操作参数制备RES纳米分散体,当RES溶液与反溶剂水溶液进料流量比为1∶20(分别为3 m L/min和60 m L/min),RES溶液水平进料时,制得的RES纳米分散体尺寸最小,平均粒径为132 nm;此时RES纳米分散体接触角为19°,水润湿性较原料药得到大幅度提高;在拟肠液(p H 7.4)环境下,RES纳米分散体在120 min内累积释放率可达到95%。在上述优化工艺的基础上利用套管式微通道反应器进行放大实验,得到套管式微通道反应器制备的RES纳米分散体颗粒尺寸更小,平均粒径为82 nm;在拟肠液环境下,所得RES纳米分散体在120 min内累积释放率可达到97%,略高于T型微通道反应器所得产品的溶出量。计算结果表明,套管式微通道反应器可显著提高处理量,约为T型微通道反应器处理量的10倍。

The preparation of resveratrol （RES） nanodispersion using an anti-solvent precipitation method in a mi- crochannel reactor has been investigated. RES nanoparticles were prepared in a T-junction microchannel reactor af- ter optimizing the operating parameters. The minimum size of the RES nanoparticles was 132 nm. The wettability of the RES was significantly improved using this method, with the contact angle of the RES nanodispersion reduced to 19°. The dissolution degree of the RES nanodispersion was 95% after 120 min in simulated human intestinal juice （pH 7.4）. To scale up, RES nanodispersion was prepared in a tube-in-tube microchannel reactor. The size of RES nanodispersion was 82 nm, smaller than that of the products prepared in the T-junction microchannel reactor. In simulated human intestinal juice the dissolution degree of RES nanodispersion was 97% after 120 min. In addi- tion, the throughput of the tube-in-tube microchannel reactor was significantly increased, being 10 times more than that of the T-junction microchannel reactor.