Enhanced Bioavailability Of Poorly Water-soluble Drugs By Transfersomes

In this study,liposomes composed of soybean phosphotidylcholine(SPC) and sodium deoxycholate(SDC),which is called transfersomes,were prepared by a dry-film dispersing method.A poorly water-soluble drug fenofibrate was taken as the model drug.Fenofibrate was determined by an HPLC-UV method.The mobile phase was composed of acetonitrile and distilled water(adjusted to pH 4 with acetic acid) in a volume ratio of 90/10(v/v) at a flow rate of 2.0 ml/min.Linearity,limit of quantification,accuracies and precisions were all suitable for in vitro determination.Some properties of the transfersomes,including particle size and entrapment efficiency,were extensively characterized.SDC/SPC ratio,the hydration phosphate buffer pH and homogenization parameters were found to affect particle size and size distribution significantly.Entrapment efficiency of fenofibrate into transfersomes was primarily dependent on the SDC/SPC ratio and the hydration medium pH.Cryo-TEM photographs demonstrated that blank and fenofibrate-loaded transfersomes retained hydrated morphology,as near spherical morphology was observed for both.Comparison of the photographs indicated no obvious changes in transfersome morphology as a result of drug-loading.The membrane fluidity of transfersomes was studied by fluorescence anisotropy measurement.The results showed that incorporation of SDC resulted in increase in the membrane fluidity of transfersomes in a dose-dependent manner,In vitro release test indicated that no more than 20%of total fenofibrate was released from transfersomes and liposomes at 2 h,in contrast with near complete release from micronized fenofibrate capsules.It concluded that incorporation of fenofibrate into liposomes did not give rise to enhanced release.Stability studies showed that storage temperature influenced transfersomes significantly,a low temperature(4℃) is suitable for transfersome,while a higher temperature(25℃,37℃) can make it unstable.Oral bioavailability of transfersomes,liposomes and Lipanthyl(?),a commercial fenofibrate product,were compared in Beagle dogs(at a dose of 30mg calculated as fenofibrate).The levels of fenofibric acid,which is the active metabolite of fenofibrate, in plasma were assayed by a validated HPLC method.Pharmacokinetic analysis was performed by means of a model-independent method using 3p97 computer program.In vivo measurements indicated that pharmacokinetics and bioavailability demonstrated higher rates of fenofibrate absorption from both transfersomes and liposomes than micronized fenofibrate.The bioavailability of transfersomes and liposomes was 5.13-and 3.28- fold higher,respectively,as compared to micronized fenofibrate. Transfersomes can be used to enhance the bioavailability of poorly water-soluable drug.Above all,a dry-film dispersing method was taken to prepare transfersomes.Several properties of the liposomes,including particle size,entrapment efficiency,membrane fluidity,in vitro release characteristics and stability were extensively characterized.The beagle dog experiments indicated that,the oral bioavailability of fenofibrate was significantly enhanced by using transfersomes compared with the fast-release formulation of micronized fenofibrate,and mechanisms other than enhanced release by transfersomes contribute to improved bioavailability.