Dihydromyricetin mixed micelles:Preparation characterization and pharmacokinetic study
Objective To prepare dihydromyricetin mixed micelles(DMY-MMs),and evaluate oral pharmacokinetic behavior and calculate its relative oral bioavailability.Methods Single factor tests were used to determine the screening interval of the main influencing factors,and Box-Behnken design-response surface methodology was employed to optimize prescriptions of DMY-MMs.Transmission electron microscope(TEM)was employed to observe its microscopic appearance.Crystal form of lyophilized powder was analyzed by X-ray powder diffraction(XRPD).Release behavior of DMY-MMs in vitro was investigated by dialysis method.SD rats in each group were administered intragastrically with dihydromyricetin and DMY-MMs,respectively.Pharmacokinetics and relative bioavailability were also compared.Results Optimal formulation of DMY-MMs:carrier to drug ratio was 7.6∶1,Soluplus to TPGS ratio was 6.4∶1,and hydration time was 2 h.Envelopment efficiency,drug loading,particle size and Zeta potential were(90.21±1.60)％,(10.43±0.21)％,(68.14±7.23)nm and(1.07±0.26)mV,respectively.Appearance of DMY-MMs was spherical,dihydromyricetin changed into an amorphous form in DMY-MMs lyophilized powder.Release behavior in vivo of DMY-MMs was in accordance with Higuchi model,and drug release equation was lnln[1/(1-Mt/M∞)]=0.639 71nt-1.781 1(r=0.978 4).Pharmacokinetics of DMY-MMs showed that t1/2was prolonged to(4.11±1.07)h,Cmaxwas enhanced to 4.41-fold and oral relative bioavailability was increased to 5.18-fold.Conclusion DMY-MMs changed pharmacokinetic behavior of dihydromyricetin in vivo and significantly promoted its oral absorption.
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