The Berberine Absorption Prediction Model Was Established To Study The Properties Of The Biopharmaceutical Classification System Of Traditional Chinese Medicine

Objective:Chinese Materia Medica is multiple compounds?The property of drug's solubility and permeability determines the rate-limiting biological availability following oral administration.This paper takes BCS-IV berberine as research objects.The purposes of this study are to characterize the effect of physiological parameters on,to study ACAT-PBPK model of oral administration of berberine in Rats,and to further define in Vivo-in Vitro Correlation.The experiments carry on by the BCS method and mathematical model,in order to discover the interaction law of high content compound and the multiple compounds environment,and also discovery the CMMBCS properties of single and complex medicines.This paper is helpful for revealing the possible research topics and existing problems in the preformulation study.and would provide leading basic for studying Biopharmaceutics Classification System of Chinese Materia Medica(CMMBCS)of multiple components.Methods:(1)Gastro PlusTM software was used to establish ACAT-PBPK model of oral administration of berberine in Rats,the effectiveness of the model was evaluated.The dissolution curve of Saled Berberine hydrochloride tablets was determined with paddle method.The model was used to simulate the absorption?tissue distribution and food effects of berberine,and might be utilized in the in vivo in vitro correlation analysis.(2)The effect of artificial multicomponent environment on the intrinsic dissolution rate(IDR)of berberine were investigated in this study,using a non-disintegrating disk.Mathematical model was built to describe the variation trend of their influence on the solubility of puerarin.Carried out with progressive levels,single component environment:puerarin,baicalin,and glycyrrhizic acid,double-component environment:puerarin and baicalin,puerarin and glycyrrhizic acid,baicalin and glycyrrhizic acid,treble-component environment:puerarin,baicalin,glycyrrhizic acid and the classic formula "Gegen Qinlian Fang" were used to describe the variation tendency of their influences on the solubility of berberine.Results:(1)Several conclusions could be drawn from the results described above,Berberine has poor absorption in the gut,and most of the oral dose remained inside the gastro-intestinal lumen.After absorption from the gastrointestinal tract,berberine could be widely distributed in the organs,while its concentration in plasma is low.The results had no significant difference for food effects.Results show that calculations are in good agreement with literature data.The data presented in this paper demonstrate that the dissolution curves were fitted with the Weibull distribution model.In this sections we will look into the estimation of drug absorption via important barriers including the gastrointestinal tract.GastroPlusTM software had a good in vitro and in vivo correlation.In vitro dissolution profile can be used instead of in vivo absorption and the in vivo behavior profile of the new formulation can also be predicted.(2)Berberine belongs to the low solubility and low dissolution.The experiments carry on by the BCS method and mathematical model,in order to discover the interaction law of high content compound and the multiple compounds environment,and also discovery the CMMBCS properties of single and complex medicines.The results of this study showed that the intrinsic dissolution rate(IDR)of berberine were dramatically different the classic formula "Ge gen Qin lian Fang".Solubility has improved,IDR>lmg·cm-2·min-1.Conclusion:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and IVIVC evaluation of berberine preparations by Gastro PlusTM software.At artificial multicomponent environment,IDR has little change,which in artificial multicomponent environment classified as CMMBCS-IV,IDR has improved in "Ge gen Qin lian Fang",changes greatly.it was classified as CMMBCS-III in"Ge gen Qin lian Fang".In this study,it can lay a foundation for studying the mechanism of compound compatibility of Chinese Materia Medica,Oral Dosage formulation and Biopharmaceutics Classification System of Chinese Materia Medica(CMMBCS).