Study On In Vitro Dissolution Test And Pharmacokinetics In Piglets Of Curcumin Solid Dispersion

Curcumin has many pharmacological effects such as anti-oxidation,anti-inflammation,anti-tumor,hypoglycemic and hypolipidemic effects.It is a rich natural product and used as a new-style feed additive.In recent years,with the improving of people’s living standard,more safe animal products are required.Curcumin has potential to be an antibiotic substitute in animal husbandry.This work studied the in vitro dissolution rate of curcumin solid dispersions and curcumin premixes,and the pharmacokinetics in healthy piglets.The best prescription of curcumin solid dispersion was screened by using the experimental parameters of dissolubility and dissolution rate by in vitro release test.The results of pharmacokinetics research provides scientific basis for further developing solid dispersion of curcumin.The in-vitro release test was conducted by Chinese Veterinary Pharmacopoeia release assay（pulp method）.Curcumin was dissolved in acetate buffer of pH 1.2（containing 0.5%Tween-80）,acetate buffer of pH 4.3（containing 0.5%Tween-80）and phosphate buffer of pH6.8（containing 0.5%Tween-80）with rotational speed of 75 r/min,respectively.Samples were assayed by HPLC-UV to calculate the cumulative release of curcumin preparations at different time points.The results showed that the cumulative dissolution of curcumin solid dispersion（batch number:20180123）reached 93.30%in acetate buffer（containing 0.5%Tween-80）at pH 4.3.And it was stable in pH 1.2 hydrochloride buffer,which indicated the destruction of curcumin was not easy degraded under the strong acid conditions.The release of curcumin can release completely within 6 h in pH 6.8 phosphate buffer（0.5%Tween-80containing medium）,which indicated the solid dispersion of curcumin can be released in pig intestine.In this study,the concentration of curcumin in swine plasma was determined by LC-MS/MS in the first time.The experiment was carried out according to a parallel design.Sixteen healthy crossbred swine were randomly divided into two groups for pharmacokinetics research of oral curcumin solid dispersion and curcumin premixed.The non-compartmental model in WinNonlin5.2.1 software was used to fit the plasma concentration-time data.The results showed that the pharmacokinetics of curcumin in piglets matched non-compartmental model after a single dose oral of 100 mg/kg curcumin solid dispersion and curcumin premix.The area under the curve（AUC）of curcumin solid dispersion was 104.53±38.67 h·ng/mL and of curcumin premix was 37.82±11.48 h·ng/mL.The peak time(T_max)of curcumin solid dispersion was 3.25±0.38 h and of curcumin premix was 2.31±0.37 h.The elimination half-life(t_1/2β)of curcumin solid dispersion was 3.55±2.17h and of curcumin premix was 6.93±0.86 h.The average residence time（MRT）of curcumin solid dispersion was 5.23±0.53 h and of curcumin premix was 4.26±0.47 h.This study compared the pharmacokinetic parameters of piglets fed with curcumin solid dispersion and curcumin premix,and showed that T_max significantly delayed,Cmax significantly increased,AUC heightened after the piglets fed the solid dispersion of curcumin.The bioavailability of curcumin solid dispersion was 276.38%.The statistical analysis showed that the AUC,T_max,C_max,t_1/2βand MRT were significantly different between the curcumin solid dispersion group and the premix group（p<0.05）.