Formulation And Evaluation Of Quercetin Nanosuspensions-loaded Orodispersible Films

Quercetin,a natural flavonoid,exists extensively in many traditional Chinese medicines such as sophorae flos,albiziae flos,platycladi cacumen.Quercetin has a variety of pharmacological activities,including anti-oxidation,anti-cancer and sedative and hypnotic effects.However,the clinical application of quercetin was seriously restricted by it’s low hydrophilicity,low lipophilic and poor absorption in the gastrointestinal tract.In this study,quercetin was chosen as a model drug.A novel ODFs containing drug NS（NS-ODFs）was developed by combining the advantages of NS and ODFs with the goals of enhancing the solubility and oral bioavailability of quercetin and improving the stability of QT-NS.In this study,the QT-NS was prepared by a miniaturized milling method.The formulation and process of QT-NS were optimized by single factor experiment,with the mean particle size and polydispersity index（PDI）as indexes.The mean particle size,PDI and Zeta potential of the QT-NS prepared by optimal technology parameters were about 210 nm,0.20,-27.5 mV respectively.SEM image displayed QT-NS was irregular granule in shape.The result of XRD indicated that the crystal state of QT in QT-NS was a little different from that of raw QT.The stability of QT-NS was poor.Sedimentation and particle growth was observed when QT-NS was stored at room temperature and dark condition for several days.In order to improve the stability of QT-NS,it was formulated to QT-NS-ODFs by solvent casting method.The formulation of QT-NS-ODFs were optimized by employing 3-factor,3-level Box–Behnken design-response surface methodology with the amount of film forming polymer（PVA 0588）,filling agent（sorbitol）and disintegrating agent（L-HPC）as investigation factors,and disintegration time,mean particle size after redispersal and folding endurance as indexes.The three indexes of the QT-NS-ODFs prepared by optimal formulation process were about 45 s,320 nm and 240 times respectively.The Zeta potential of QT-NS-ODFs was significantly lower than that of QT-NS.QT-NS-ODFs was with uniform drug,in which the QT nanoparticles of about 300 nm in size were dispersed well.Moreover,the result of XRD indicated that the crystal state of QT in QT-NS-ODFs was a little different from that of raw QT.In the in vitro release test,QT-NS-ODFs showed an increased release velocity markedly.Moreover QT-NS-ODFs exhibited good stability when stored at room temperature and dark condition for 60 days.The pharmacokinetics of QT-NS-ODFs in rats was studied in this paper.Compared to raw QT,the C_max from QT-NS and QT-NS-ODFs was increased by363.59%and 389.91%,respectively,and the AUC_0-∞from them was increased by608.35%and 576.13%,respectively.The results indicated QT-NS and QT-NS-ODFs were more easily absorbed and could significantly improve the bioavailability of QT.