摘要
目的制备根皮素纳米混悬剂,并考察其体内药动学。方法单因素试验筛选稳定剂种类、比例、用量、超声功率、超声时间,测定粒径、Zeta电位、载药量、溶解度、体外释药。12只大鼠分别灌胃给予根皮素及其纳米混悬剂的0.5%CMC-Na溶液(100 mg/kg),于0.167、0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC法测定根皮素血药浓度,计算主要药动学参数。结果最佳条件为稳定剂(PVP K30-泊洛沙姆188)比例1∶1,稳定剂用量40 mg,超声功率350 W,超声时间30 min,平均粒径为167.2 nm,PDI为0.138,Zeta电位为-36.4 mV,载药量为59.60%,溶解度为867.35μg/mL,45 min内累积溶出度接近100%。与原料药比较,纳米混悬剂t_(max)缩短(P<0.05),C_(max)、AUC _(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度增加至3.47倍。结论纳米混悬剂可改善根皮素溶出度和口服生物利用度。
AIM To prepare phloretin nanosuspensions and to investigate their in vivo pharmacokinetics.METHODS Single factor test was used to screen the type,ratio and consumption of stabilizer,ultrasonic power and ultrasonic time,after which the particle size,Zeta potential,drug loading,solubility and in vitro drug release were determined.Twelve rats were given intragastric administration of 0.5%CMC-Na solutions of phloretin and its nanosuspensions(100 mg/kg),respectively,after which blood collection was made at 0.167,0.25,0.5,1,1.5,2,3,4,6,8,12 h,HPLC was adopted in the plasma concentration determination of phloretin,and main pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 1∶1 for stabilizer(PVP K30-Poloxamer 188)ratio,40 mg for stabilizer consumption,350 W for ultrasonic power,and 30 min for ultrasonic time,the average particle size,PDI,Zeta potential,drug loading and solubility were 167.2 nm,0.138,-36.4 mV,59.60%and 867.35μg/mL,respectively,and the accumulative dissolution rate within 45 min reached 100%.Compared with raw medicine,the nanosuspensions demonstrated shortened t_(max)(P<0.05)and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),and relative bioavailability was enhanced to 3.47 times.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of phloretin.
作者
张伟利
决利利
李晓婷
ZHANG Wei-li;JUE Li-li;LI Xiao-ting(Zhengzhou University of Industrial Technology,Zhengzhou 451150,China)
出处
《中成药》
CAS
CSCD
北大核心
2021年第11期2933-2938,共6页
Chinese Traditional Patent Medicine
基金
河南省科技攻关项目(202102310417)。
关键词
根皮素
纳米混悬剂
制备
体内药动学
HPLC
phloretin
nanosuspensions
preparation
in vivo pharmacokinetics
HPLC
