Study Of In Vivo Pharmacokinetics In Rats And Dissolution Of Hanbiting Tablets

Objective Hanbiting tablets were recorded into Traditional Chinese Medicine Patent Prescription by SFDA,mainly used in the treatment of diseases such as rheumatism,rheumatoid arthritis or periarthritis of shoulder,which have better anti-inflammatory and analgesic effect.Presently,we have none viewed about in vivo pharmacokinetics of Hanbiting tablets in rats and their scientificity and clinical safety of compound preparation compatibility reported.In vivo and in vitro experiments were carried out with Hanbiting tablets to investigate pharmacokinetic process,to understand if prescription factor has impact on in vivo process of the nux vomica powder in Hanbiting tablets.With nux vomica powder as reference,experiments provide certain reference basis on preparation technology,quality control and clinical application of rationality and scientificity for Hanbiting tablets.Methods(1)In vivo pharmacokinetic study of Hanbiting tablets and nux vomica powder in rats.Pharmacokinetic model was set up With oral administration and vena ophthalmica sampling approach to rats.UPLC/MS/MS was used for determination of brucine and strychnine and pharmacokinetic parameters of them were computed by DAS2.1 software to discuss plasma concentration-time profiles of Hanbiting tablets in rats.(2)Compatibility research of nux vomica powder on the influence of in vivo small intestine absorption in rats.With in vivo rat single-pass intestinal perfusion model and determination of brucine and strychnine by HPLC,the absorption rate constant(Ka)and the effective permeability coefficient(Peff)of each group were calculated.To investigate influence of compound compatibility on intestinal absorption of brucine and strychnine in rats.(3)In vitro determination of dissolution rate of the nux vomica powder in Hanbiting tablets.With dissolution rate of brucine and strychnine as index,and investigate preparation conditions such as dissolution medium,rotational speed,sampling time points.Contents were determined by HPLC to study the influence of dosage form on in vitro dissolution,compared with nux vomica powder.Results(1)Contents of brucine and strychnine were determined by UPLC-MS/MS in the nux vomica powder and Hanbiting tablets in rat plasma.Pharmacokinetic parameters were calculated by DAS2.1 Software.Main pharmacokinetic parameters of brucine and strychnine in Hanbiting tablets were as follows: the peak time(tmax)were 47.5,24.7 min,the peak concentration(Cmax)7.8,26.7 ng·min-1,the area under the curve(AUC0?t)990,4 170 ng·min·L-1,clearance rate(CL/F)3 846,746 L·kg-1·min-1 and in nux vomica powder were : tmax55,42.5 min,Cmax 8.8,33.3 ng·min-1,AUC0?t 941 and 3 301 ng·min·L-1,CL/F 449,507 L·kg-1·min-1,respectively.(2)The result of small intestine absorption in rats with single-pass intestinal perfusion mode were that brucine and strychnine are easily absorbed through the intestinal wall in Hanbiting tablets group,nux vomica powder group and other groups,and the best absorption bowel was jejunum.Ka and peff of brucine and strychnine in Hanbiting tablets compound compatibility group,for example radix rehmanniae,caulis sinomenii,epimedium,garter snake,were significantly higher than nux vomica powder group.It was discussed from Angle of intestinal absorption of brucine and strychnine in different compatibility,and it verified the pharmacokinetic results in rats preliminarily.(3)Dissolution method of experiment established had significant correlation with pharmacokinetic absorption phase in vivo.Dissolution rate of nux vomica powder and mixture were significantly higher than Hanbiting tablets within 30 mins,but they were flat of the cumulative dissolution rate after 60 mins.Conclusion(1)The Pharmacokinetic behavior of brucine and strychnine was well fitted to two-compartment model in rats.Compared with nux vomica powder,Hanbiting tablets can significantly accelerate the absorption and elimination rate of brucine and strychnine and improve the oral bioavailability of strychnine.(2)Compound compatibility of nux vomica power have significantly influence on intestinal absorption in rats.(3)Dosage form can significantly postpone in vitro dissolution of nux vomica powder in Hanbiting tablets,Dissolution method of experiment established had significant correlation with the body in vivo and is suitable for determination of dissolution of Hanbiting tablets in vitro.