目的 采用超临界流体抗溶剂技术(supercritical anti-solvent, SAS)制备难溶性药物水飞蓟素(silymarin,SM)纳米颗粒(nanoparticle),改善其体外释放行为。方法 单因素考察压力、温度、进样流速、药物浓度对纳米颗粒粒径和沉淀率的影响,并采用扫描电镜(SEM)、差示扫描量热法(DSC)、X-射线衍射法(XRD)等进行表征。评价水飞蓟素纳米颗粒的体外溶出行为。结果 优选纳米颗粒制备条件为:压力15 MPa,温度35 ℃,进样流速1.5 mL·min-1,溶液质量浓度100 mg·mL-1。X-射线衍射法与差示扫描量热法分析显示,经超临界流体抗溶剂技术将水飞蓟素原药粉制备成水飞蓟素纳米颗粒后,其结晶度减小并转变为无定型态。体外溶出实验结果显示,其累积释放度在10 min内达到80%以上,显著高于原药粉和市售制剂益肝灵。结论 超临界流体抗溶剂技术制备的水飞蓟素纳米颗粒粒径显著减小,能显著提高药物的体外溶出度。
Abstract
OBJECTIVE To enhance dissolution rate of silymarin (SM) by forming SM nanoparticles (SM-NA) with supercritical anti-solvent (SAS) method. MOTHODS Single-factor test was employed to investigate the influencing factors of particle size and yield of SM-NA, such as pressure, temperature, flow rate, and concentration of the solution. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) were used to determine the state of SM-NA. The dissolution characteristics in vitro were investigated with 0.3% SDS aqueous solution as the solvent and compared with the SM powder. RESULTS Taking size distribution as well as yield of SM-NA as the evaluation indexes, the optimal prepration parameters were selected as followings:pressure 15 MPa, temperature 35 ℃, flow rate 1.5 mL·min-1, concentration 100 mg·mL-1. The XRD and DSC of SM-NA described the decrease of SM in crystallinity, and it was transformed mostly with the amorphous state, compared with the SM powder. The accumalte release rate of SM-NA achieved 80% within 10 min, markedly higher than that of the SM powder and its commercial preparation. CONCLUSION The SM-NA prepared by SAS has remarkablly smaller particle size thus can greatly improve the in vitro release of SM.
关键词
水飞蓟素 /
超临界流体抗溶剂技术 /
纳米颗粒 /
溶出度
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Key words
silymarin /
supercritical anti-solvent (SAS) /
nanoparticle /
in vitro release
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中图分类号：
R944
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参考文献
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脚注
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基金
教育部博士点基金资助项目(20123107110005)
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