Preparation and in vivo pharmacokinetics of cucurbitacin B nanosuspensions
10.3969/j.issn.1001-1528.2023.12.002
- VernacularTitle:葫芦素B纳米混悬剂制备及其体内药动学研究
- Author:
Rong CHEN
1
;
Li TIAN
;
Xiao-Fei XUE
;
Si-Ying PAN
;
Xue YANG
;
Qing TIAN
Author Information
1. 郑州澍青医学高等专科学校,河南 郑州 450064
- Keywords:
cucurbitacin B;
nanosuspensions;
preparation;
in vivo pharmacokinetics;
high-pressure homogenization method;
UPLC-MS/MS
- From:
Chinese Traditional Patent Medicine
2023;45(12):3872-3878
- CountryChina
- Language:Chinese
-
Abstract:
AIM To prepare cucurbitacin B nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method.With stabilizer type,stabilizer-drug ratio and homogeneous frequency as influencing factors,particle size and PDI as evaluation indices,the formulation was optimized by single factor test,after which the solubility and stability were determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of cucurbitacin B,physical mixture and cucurbitacin B nanosuspensions(10 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,8,10,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of cucurbitacin B,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was hydroxypropyl cellulose+sodium dodecyl sulfate(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-drug ratio,80 MPa for homogeneous pressure,and 12 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 200 nm,0.140 and-32 mV,respectively.The nanosuspensions demonstrated obviously higher solubility than that of raw medicine and physical mixture,along with good stability within 6 months.Cucurbitacin B existed in the nanosuspensions in an amorphous state.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened tmax(P<0.01),prolonged t1/2(P<0.05,P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 4.32 times as compared with that of raw medicine.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of cucurbitacin B.
