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目的采用超临界辅助喷雾制粒法制备固体脂质纳米粒,并考察工艺与处方因素对纳米粒理化性质的影响。方法采用自制超临界喷雾制粒设备,制备硬脂酸脂质纳米粒,考察硬脂酸浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径等对固体脂质纳米粒粒径的影响,筛选合适的处方工艺参数;以亲水性大分子药物胰岛素为模型药物,制备载药固体脂质纳米粒,评价纳米粒的粒径、电位、包封率、释放度等理化性质。结果制备得到的纳米粒粒径与载体浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径有关,通过处方工艺的调节,可制得平均粒径<300 nm的固体脂质纳米粒;制得的胰岛素固体脂质纳米粒的平均粒径约300 nm,包封率72.2%,载药量为3.44%,载药纳米粒在体外可实现12 h缓慢释放;处方中加入泊洛沙姆可减小纳米粒粒径和粒度分布,但药物的包封率降低,并且突释现象更明显。结论超临界辅助喷雾制粒法可用于固体脂质纳米粒的制备,并能够对亲水性药物实现有效的包封和释放的调节。
OBJECTIVE To prepare solid lipid nanoparticles by spray-granulation with supercritical fluid and study the influence of technology and prescription on the physico-chemical properties of nanoparticles. Methods The self-made supercritical spray granulation equipment was used to prepare stearic acid lipid nanoparticles. The effects of the concentration of stearic acid, the flow ratio of CO2 to carrier solution and the diameter of nozzle on the particle size of solid lipid nanoparticles were investigated. The appropriate formulation parameters were determined. The hydrophilic macromolecular drug insulin was taken as the model drug to prepare solid lipid nanoparticles for drug loading. The physical and chemical properties such as particle size, potential, entrapment efficiency and release rate were evaluated. Results The nanoparticle size and carrier concentration, supercritical fluid CO2 and carrier solution flow ratio and nozzle diameter were related to each other. Through the adjustment of prescription, solid lipid nanoparticles with average particle size <300 nm could be obtained. The average diameter of insulin-loaded lipid nanoparticles was about 300 nm, the entrapment efficiency was 72.2% and the drug loading was 3.44%. The drug-loaded nanoparticles could be slowly released in vitro in 12 h. Small particle size and particle size distribution, but the drug encapsulation efficiency decreases, and the burst phenomenon is more obvious. Conclusion The supercritical-assisted spray granulation method can be used for the preparation of solid lipid nanoparticles and can regulate the effective encapsulation and release of hydrophilic drugs.