The Study Of Preparation And Bioavailability For Freeze-dried Albendazole Nano-liposome

Objective:To prepare the freeze-dried albendazole nano-liposome based on the albendazole liposome(L-ABZ),in order to increase stability,improve the bioavailability,and lay a foundation for the selection and application of new dosage forms.Methods:Laser scattering method and glucan gel column chromatography,respectively determine the particle size and entrapment efficiency of albendazole nano-liposome(NL-ABZ).Both of them as the evaluation index for high pressure homogeneous and freeze-drying technique.The primary stability test was carried on.Established a high performance liquid chromatography(HPLC)determination of plasma concentration method of albendazole and its metabolites.Compared with albendazole tablet(T-ABZ)and L-ABZ,evaluated the relative bioavailability(Frei)of freeze-dried NL-ABZ in rats.Results:1)The best dispersion system by laser scattering method is:tween 80:ABZ liposome for the volume of 4:1,20 times dilution by 0.9%sodium chloride solution.2)The optimal experimental conditions for preparing NL-ABZ by high pressure homogeneous technology:the pressure is 20000 psi,cycle 6 times,the temperature is 40℃.The average particle size is under 210nm,which is in the nano size range and far less than L-ABZ.3)The best technology parameters of preparing freeze-dried NL-ABZ is:-35℃ quick frozen 18h,dried 48h,plus a total concentration of 16%included glucose and mannitol(4:6).4)The stability test:freeze-dried NL-ABZ is better than that of L-ABZ under the condition of 4℃,which could store for 12 months with good physical and chemical properties under the condition of-18℃.5)The HPLC determination of ABZ and its metabolite in plasma,which conformed to the requirements of the methodology.6)Animal experiment results showed that freeze-dried NL-ABZ produced higher relative bioavailability than T-ABZ and L-ABZ group(Frel is 236.04%and 178.45%respectively).Conclusion:The preparation of freeze-dried NL-ABZ process is feasible and reproducible.The stability and relative oral bioavailability is better than that of L-ABZ,which provided some experimental basis for later research and development.