Preparation and evaluation of phloretin and valsartan co-amorphous
Objective Phloretin(PT)is an insoluble drug with low oral bioavailability.It is proposed to improve its dissolution rate by preparing co-amorphous(CA)with valsartan(VST),so as to improve its oral bioavailability.Methods CA was prepared by spray drying method with VST as drug carrier and PT as model drug.Fourier infrared spectroscopy(FT-IR)was used to observe the structure of functional groups and the intermolecular forces of the samples.The glass transition temperature(Tg)was determined by differential scanning calorimetry(DSC)to further verify the interaction between PT and VST molecules.The crystallographic properties of powder were observed by X-ray diffraction(PXRD).The microstructure of the sample was observed by scanning electron microscopy(SEM).Investigate the intrinsic dissolution of drugs in simulated gastric and intestinal fluids,and calculate the dissolution rate(IDR);Assess the stability of CA under high temperature and different humidity conditions;Investigating the pharmacokinetics of CA and PT(200 mg·kg-1)in rats.Results FT-IR and DSC show that there is a strong interaction force between PT and VST in CA,and PXRD and SEM show that CA is amorphous,indicating that PT and VST are co-sprayed to form eutectic amorphous.The dissolution rate of CA is significantly higher than that of PT(P＜0.05).The oral bioavailability in vivo was 4.12 times higher than that of the bulk drug,and the Cmax was 7.44 times higher.CA showed good stability at high temperature(50±2)℃,but poor wet stability.Conclusion The CA prepared by PT and VST can obviously improve the dissolution rate and oral bioavailability of PT,and has good thermal stability.
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