摘要
目的优化叶黄素酯(LE)纳米粒(NPs)的制备工艺,并对其水溶性的改善程度进行测试。方法以四氢呋喃为溶剂,去离子水为反溶剂,泊洛沙姆188作为表面活性剂,通过反溶剂法制备LE-NPs,采用单因素实验设计法优化LE-NPs制备工艺。并综合利用扫描电子显微镜、激光粒度仪、X射线衍射、差示扫描量热法等分析方法对获得的LE-NPs理化性质进行表征;采用气相色谱(GC)进行溶剂残留测定;并进行了体外溶出对比实验。结果 LE-NPs的最优制备条件为沉积时间10 min,叶黄素酯质量浓度50 mg/mL,溶剂反溶剂体积比为1∶7,泊洛沙姆188质量分数0.5%,搅拌速率950 r/min,沉积温度25℃;所得LE-NPs为球形,平均粒径为164 nm,其中四氢呋喃残留量为344.3μg/g,低于人用药物注册技术要求国际协调会(ICH)要求的最低标准(0.780 mg/g);在人工胃液环境中LE-NPs的饱和溶解度和溶出速率分别是原药的2.91倍和9.65倍。结论反溶剂法制备的LE-NPs具有较好水溶性,在口服制剂中具有潜在的用途。
Objective To prepare lutein ester（LE） nanoparticles（LE-NPs） by anti-solvent method using tetrahydrofuran as solvent, deionized water as antisolvent and Poloxamer 188 as surfactant, and to optimize the process of getting LE-NPs. Methods The concentration of LE, ratio of solvent to solvent, type and dosage of surfactant, precipitation time and stirring speed were investigated factors affecting the particle size of LE-NPs. The raw LE and LE-NPs were observed and analyzed by scanning electron microscopy, laser particle size analyzer, X-ray diffraction, and differential scanning calorimetry; Solvent residue was tested by GC method. What＇s more, the solubility and dissolving capability of raw LE and LE-NPs also were detected in vitro in this study. Results The optimized preparation conditions of LE-NPs were as follows： 10 min of stirring time, 50 mg/mL of LE concentration, 1∶7 of the volume ratio of solvent to antisolvent, 0.5% at mass fraction of poloxamer 188, 950 r/min of stirring speed, 25 ℃ of precipitation temperature. The mean particle size of spherical LE-NPs was 164 nm. XRD and DSC results showed that LE-NPs had lower crystallinity compared to raw drug, and mainly in amorphous state. The solvent residue result showed that tetrahydrofuran residue content in LE-NPs was 344.3 μg/g. Furthermore, the solubility and dissolution rate of LE-NPs were about 2.91 times and 9.65 times of raw LE. Conclusion LE-NPs prepared by antisolvent method could become a new formulation, which has higher solubility and bioavailability than raw LE.
出处
《中草药》
CAS
CSCD
北大核心
2017年第14期2870-2876,共7页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(21473023)
关键词
叶黄素酯
纳米粒
反溶剂法
单因素优化
粒径
饱和溶解度
溶出
lutein esters
nanoparticles
antisolvent method
single factor optimization
particle size
saturation solubility
dissolution
