超临界辅助喷雾法用于固体脂质纳米粒的制备

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〈300nm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300nm，包封率72．2％，载药量为3．44％，载药纳米粒在体外可实现12h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。

Supercritical Assisted Atomization for Preparation of Solid Lipid Nanoparticles

OBJECTIVE To prepare the solid lipid nanoparticles(SLN) via supercritical assisted atomization(SAA) and investigate the effect of formulation and process on physicochemical characteristics of nanoparticles (NPs). METHODS With self-made SAA particle-producing equipment, stearic acid(SA) based SLN was produced, and the effect of SA concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle, on particle size of SLN were investigated to discover the appropriate process conditions. SLN loading insulin, a hydrophilic macromolecule drug, was produced and their physicochemical characteristics was observed, such as size, zeta-potential, entrapment efficiency(EE) and drug-loading ratio(DL). RESULTS Particle size of NPs was depended on material concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle. SLN with mean size <300 nm were obtained through formulation and process adjustment during preparation. Insulin-loaded SLN with mean size of about 300 nm, EE 72.2% and DL 3.44% was obtained, which released drug slowly during 12 h in vitro. Poloxamer-modified formulation made SLN with reduced size and distribution range, meanwhile the drug EE was decreased and burst-release was significant. CONCLUSION SAA is successfully applied to produce SLN and hydrophilic-drug-loaded SLN with modified releasing profile.