Preparation And Evaluation Of Daidzein Capsule Based On Nanosuspension Technique

Objective: Daidzein(DZ)is effective in the treatment of different kinds of cardiovascular diseases,hypertension and atherosclerosis.However,its extremely low oral bioavailability that mainly caused by the poor solubility either in aqueous or oil phase restricted its oral applications.To improve the solubility,we prepared daidzein nanosuspensions,and enhanced the stability of the nanosuspension system by lyophilization and capsuling.Methods: High pressure homogenization method(Top)and precipitation combine high pressure homogenization method(Combine)were used to prepare the nanosuspensions.Orthogonal design method was utilized to complete the optimization and screen of Daidzein nanosuspensions formulation,in the meantime the average particle size and zeta-potential were selected as the investigate index.The amount and type of stabilizers were investigated.Daidzein nanosuspension capsule was made from the freeze-dried powder.Solubility study and dissolution test were determined by HPLC compared with commercial products,intestinal absorption study was confirmed by recording the accumulative amount of DZ in 2 hours and oral bioavailability was examined through pharmacokinetic study.Results: The results of these experiments indicated that we successfully prepared two daidzein nanosuspension powder(DZ-NP(Top),DZNP(Combine))and its capsule with two methods.The average particle size of DZ-NP(Top)and DZ-NP(Combine)stabilized at 304±20nm and 180±15nm,respectively;zeta-potential was-28.34 mV.Furthermore,the DZ-NP(Top)increased the aqueous solubility of DZ by 5.33-fold,the ultimate accumulative amount of DZ-NP(Top)through rat small intestinal in 2 hours was approximately 1.62-fold and the oral bioavailability was enhanced 5.53-fold;the DZ-NP(Combine)increased the aqueous solubility of DZ by 5.64-fold,the ultimate accumulative amount of DZ-NP(Combine)through rat small intestinal in 2 hours was approximately 2.02-fold and the oral bioavailability was enhanced 5.93-fold,compared with pure daidzein.Conclusion: The high pressure homogenization technology and precipitation combine high pressure homogenization technology employed to prepare daidzein nanosuspensions is feasible.Daidzein nanosuspensions can significantly improve the dissolution rate and oral bioavailability compared to the commercial products.