摘要
目的:制备柠檬苦素纳米混悬剂及其冻干粉末,并进行体外评价。方法:以纳米混悬剂粒径为指标,单因素考察投药量、稳定剂用量、大豆磷脂(SPC)占稳定剂的比例等影响。采用Box-Behnken响应面法优化柠檬苦素纳米混悬剂的处方工艺,测定粒径及Zeta电位,并采用扫描电镜法观察纳米粒子形貌。冷冻干燥法制备柠檬苦素纳米混悬剂冻干粉,X射线粉末衍射法分析存在状态,平衡法测定溶解度,透析袋法评价其体外溶出度。结果:柠檬苦素纳米混悬剂最佳处方为:投药量为30 mg,稳定剂用量为88 mg,大豆磷脂占稳定剂比例为60%。平均粒径为(187.29±6.46)nm,与Box-Behnken响应面法预测值接近。Zeta电位值为(-31.58±1.77)mV,柠檬苦素纳米粒子外貌为球形或类球形。X射线粉末衍射法结果显示柠檬苦素纳米混悬剂冻干粉中以无定型状态存在,溶解度提高至95.63倍,纳米混悬剂在240 min累积溶出度达到96.11%。结论:将柠檬苦素制备成纳米混悬剂冻干粉可以提高其溶解度和溶出度,为进一步临床开发奠定了基础。
OBJECTIVE To prepare limonin nanosuspension and lyophilized powder,and perform in vitro evaluation.METHODS Particle size was employed as the evaluation index,and the effects of drug dosage,stabilizer amount and ratio of soybean phospholipids(SPC) in stabilizer on particle size were investigated by single factor analysis.Box-Behnken response surface design method was employed to investigate the optimal formulation of limonin nanosuspension,and particle size and Zeta potential were determined.Morphology of limonin nanosuspension was observed by a scanning electron microscope(SEM).Lyophilized powder of limonin nanosuspension was prepared by freeze-drying method.The presence state was analyzed by X-ray powder diffraction(XRPD).Solubility and dissolution of limonin nanosuspension were determined by balance method and dialysis bag method,respectively.RESULTS The optimal formulation of limonin nanosuspension was as follows:drug dosage was 30 mg,stabilizer amount was 95 mg,and SPC ratio in stabilizer was 60%.The average particle size was(187.29±6.46) nm,which was close to that of predicted value.The average Zeta potential was(-31.58±1.77) mV.The appearance of limonin nanosuspension was spherical or nearly spherical.Limonin was an amorphous form in nanosuspension lyophilized powder.The solubility of limonin in nanosuspension lyophilized powder was enhanced to 95.63 times,and the cumulative dissolution reached 96.11% in 240 min.CONCLUSION The solubility and dissolution of limonin can be improved by preparing limonin nanosuspension lyophilized powder,which lays the foundation for further clinical development.
作者
王柯静
决利利
常宝珠
周珊珊
焦迪
范明松
WANG Kejing;JUE Lili;CHANG Baozhu;ZHOU Shanshan;JIAO Di;FAN Mingsong(Zhengzhou University of Industrial Technology,Henan Zhengzhou 451150,China;Shanghai Institute of Traditional Chinese Medicine,Shanghai 201401,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第13期1471-1478,共8页
Chinese Journal of Hospital Pharmacy
关键词
柠檬苦素
纳米混悬剂
冻干粉
溶解度
溶出度
limonin
nanosuspensions
lyophilized powder
solubility
dissolution
