Linesinine Solid Dispersion And The Inclusion Of The Preparation And Pharmacokinetics In Rats

Objective:Liensinine is a kind of alkali indissolvable drug,its oral bioavailability is low.In order to solve the problem,this paper USES the solid dispersion technology and inclusion technology for changing the state of being in the drugs and improving the drug dissolution performance,so as to improve its bioavailability in vivo and lay the foundation for Liensinine preparations and new researchs.Method:1,Craft:By single factor experiment,optimizing the solid dispersions of carrier materials,binding materials and preparation methods of clathrate;Through orthogonal test optimization of solid dispersions and inclusion compound preparation;The determination of the drug-polymer interactions.2,Structure characterization:By means of X-ray diffraction,infrared spectroscopy,differential thermal scanning method,the microscopic imaging method of solid dispersions and the structure of the inclusion compound were characterized.3,Bioavailability studies in mice:To establish HPLC method determination of Liensinine content in whole blood,Liensinine solid dispersions and inclusion compound in rats pharmacokinetics and bioavailability in vivo.4,Solubilization comparison:Cumulative dissolution percentage as indicators.Results:1,The best preparation technology for liensinine solid dispersions:PVP K30-as carrier material,liensinine solid dispersions prepared by solvent method,the optimum prescription and preparation conditions:Liensinine and carrier for:1:1;The mixing time is:30 min;The amount of methanol 30 ml;To measure its drug loadings was(5.41 +0.30)mg/g;The best preparation technology for Liensinine clathrate:with HP-beta-CD as a carrier material and adopts saturated aqueous solution preparation of inclusion compound,the optimum prescription and preparation conditions:lotus nut alkali and HP-beta-CD ratio of 1:2,stirring time is 4 h,water bath temperature is 50 ℃;To measure its drug loadings was(4.02 ± 0.20)mg/g.2,by micro electron microscope scanning,X-ray diffraction,infrared,differential thermal scanning method on liensinine solid dispersions and inclusion compound have been characterized,results show that the Liensinine to amorphous state exists in solid dispersions and inclusion compound.3,through the rat in vivo pharmacokinetic study of solid dispersions,clathrate,lotus nut alkali AUC were(606.701±34.512)mg/(L*h),(489.800 ± 29.181)mg/(L*h),(343.900±16.311)mg/(L*h),Cmax was(28.755±0.832)ug/ml,(26.331±5.082,(22.772 ± 1.691)ug/ml,Tmax was(0.433 ±0.067)h,(0.592±0.108)h,(1.361±0.133)h.4,Solubility experiment shows that the Liensinine preparation into solid dispersion and its solubility increases after the inclusion compound,the order for Liensinine solid dispersions>Liensinineclathrate>API.In vitro dissolution,in 45 min,solid dispersion,inclusion compound,active pharmaceutical ingredients,its cumulative dissolution percentage were 88.02%,73.06%,18.66%in vitro,the liensinine preparation into solid dispersion and inclusion compound,its dissolution has greatly improved in vitro,and the liensinine dissolution percentage do significant test,solid dispersions is better than that of active pharmaceutical ingredients(p<0.01);Clathrate is better than that of active pharmaceutical ingredients(p<0.01).Conclusion:The solid dispersions and inclusion compound preparation technology is simple,feasible and reproducible;High performance liquid chromatography and ultraviolet spectrophotometry method accurate,sensitive and rapid;Liensinine in solid dispersions and inclusion compound alkali in the amorphous state of exist;Drug preparation into solid dispersions and inclusion compound can improve the drug dissolution and bioavailability;Solid dispersion technology of lotus nut alkali solubilization effect is strong inclusion technology.