| Objective:To improve the oral bioavailability of rhubarb anthraquinxones（RhA）and the stability of RhA loaded liquid self-microemulsifying delivery system by optimally designing and preparing rhubarb anthraquinones self-microemulsifying oral tablets（RhA-SET）.Methods:Adsorbent with excellent adsorption capacity was preliminarily selected by measuring the adsorption amount of concentrated RhA loaded self-emulsifying drug delivery system（ConRhA-SEDDS）by different adsorbents.The selected adsorbent was mixed with ConRhA-SEDDS at a ratio of 1:1（w/w）to obtain self-microemulsifing powder.The suitable adsorbent was finally confirmed by measuring the fluidity of the powder and the mean diameter size（MDS）,zeta potential（ZP）and polydispersity index（PDI）after self-emulsification in purified water.The interaction between the adsorbent and ConRhA-SEDDS was analyzed by powder X-ray diffraction and Fourier transform infrared spectroscopy.A two-factor-five-level central composite design combined with response surface method was carried out to attain optimal RhA-SET formulation.The MDS,ZP and PDI of RhA-SET after self-emulsification was determined by dynamic light scattering method and the droplet morphology was observed by transmission electron microscopy.The content of RhA was determined by high performance liquid chromatography-fluorescence detection.The in vitro release mechanism and in vivo oral pharmacokinetics in rabbits of RhA-SET and RhA general tablets was comparatively studied.Results:Neusilin US2 had the highest adsorption capacity for ConRhA-SEDDS,and its interaction with ConRhA-SEDDS was physical mixing.The optimized RhA-SET formulation consisted of 47%ConRhA-SEDDS,47%Neusilin US2,5%PVPP and 1%magnesium stearate.The friability of RhA-SET was 0.3894±0.0069%,the disintegration time was 5.13±0.14 min and the cumulative dissolution rate within 4 h was 87.91±1.89%.The measured value was close to the predicted value and the deviation was less than 5%.The general characteristics of RhA-SET were in line with the requirements of the Chinese Pharmacopoeia for ordinary tablets.The morphology of the droplets was spherical,and the MDS was 25.37±0.55 nm,ZP was-11.9?2.04 mV and PDI was 0.30?0.01.In vitro release of RhA-SET and RhA general tablets were both fitted to the first order kinetics.Compared with the RhA general tablets,the absorption of RhA in RhA-SET was faster,the peak time was shortened,the peak concentration and bioavailability were significantly improved,and the elimination was lower.Notably,the RhA peak concentration and area under plasma concentration-time curve(AUC0-?)in the RhA-SET group were 6.61 times and 4.45 times than that of the RhA general group,respectively.Conclusions:The design and preparation of RhA-SET is reasonable and feasible,and RhA-SET can effectively improve the bioavailability of RhA and the stability of RhA nanoemulsion. |
