Preparation And Characterization Of Solid Dispersions Of Mangiferin And Its Inclusion Complexes

Objective : Mangiferin(Mangiferin,MGF)is a glycoside with Xanthone structure,MGF water soluble and fat soluble are not conducive to gastrointestinal absorption.This paper uses of cyclodextrins and solid dispersion technology of MGF was modified to improve MGF solubility and permeability,further improve the bioavailability,to provide the experimental basis for the research on improving the mangiferin preparation application development.Methods:(1)with PVP-k30 and PEG4000 as the carrier,by solvent method according to MGF and carrier quality than 1:2,1:4,1:9And 1:18 in preparation of mangiferin PVP solid dispersion(MGF-PVP),and by the different molar ratio of preparation of mangiferin beta cyclodextrin inclusion(MGF-beta CD),mangiferin Hp-beta-CD package compound(MGF-Hp-CD).The samples were characterized by differential scanning calorimetry(DSC),X ray diffraction(XRD)and Fu Liye infrared spectroscopy(FT-IR).(2)The establishment of MGF solid dispersion and its inclusion compound HPLC content determination method of MGF solid dispersion and inclusion of MGF-PVP,MGF-PEG,CD and MGF-Hp-MGF-beta beta CD solubility,dissolution rate and apparent oil-water partition coefficient determination.(3)To determine the concentration of MGF-PVP(1:4)and MGF-Hp-beta CD(1:3)in human intestinal flora at different time points,and to investigate the metabolism of MGF solid dispersions and their inclusion substances in human intestinal flora environment.(4)SD rats were given intragastric administration of MGF and MGF-PVP(1:4).The concentrations of MGF in serum of rats at different time points were measured by HPLC,and the bioavailability of MGF and MGF-PVP in SD rats was investigated.Result :(1)DSC showed that the MGF solid dispersions and their inclusion compounds were smaller or shifted left than the peaks of the melting peaks and the excipients of the mangiferin materials,and the melting point peaks decreased with the increase of the proportion of excipients.XRD shows that the diffraction peaks of mangiferin in MGF solid dispersions and their inclusion complexes decrease or disappear with the increase of the proportion of excipients.FT-IR tips,C=O telescopic MGF solid dispersion of mangiferin and its molecular inclusion absorption peaks,O-H stretching vibration absorption peak is obviously red shifted,mangiferin and auxiliary molecules characteristic peaks are red shifted hydroxyl or disappeared.(2)MGF solid dispersion and inclusion significantly improved in water solubility,dissolution rate compared with the raw materials of mangiferin were MGF-PVP and MGF-Hp-beta CD solubility increased significantly,MGF-PVP(1:9)and MGF-Hp-CD(1:3)beta solubility increased 600 times;each time point according to the comparison of the content of MGF MGF solid dispersion and inclusion the dissolution rate of the MGF-PVP and MGF-Hp-beta CD dissolution rate and the proportion of materials was positively related to MGF-PVP,MGF-Hpand beta CD in each time point 5-120 min and MGF crude drug dissolution were significantly improved,120 min MGF-PVP and MGF-Hp-beta CD dissolution rate reached 100%.Because the water solubility of MGF solid dispersions and their inclusion compoundsincreased,the oil water partition coefficient of mangiferin decreased and the hydrophilicity increased.(3)MGF and MGF-PVP(1:4)in isolated human intestinal bacteria cultured in 2,4,5,6,7,8 hours remaining percentage,with statistical difference(P<0.01);MGF-Hp--CD and MGF beta remaining percentage comparison was not statistically significant.The performance of MGF-PVP solid dispersion against human intestinal flora metabolism was better than that of MGF-Hp-beta-CD inclusion.After MGF solid dispersion treatment,the metabolic rate of MGF decreased.(4)In this paper,the HPLC method was established to determine the concentration of SD and MGF-PVP in rats after administration of MGF,and the accuracy and precision of the method were in accordance with the requirements of the method.The pharmacokinetic experiment results show that MGF and MGF-PVP each time point of blood drug concentration had significant difference(P<0.01),MGF AUC0-12h109.26 g/mL MGF-PVP AUC0-12 h 381.22 g/mL,the average bioavailability of MGF-PVP is 3.49 times that of MGF,that of mangiferin prepared PVP solid dispersion bioavailability significantly increased.Conclusion:(1)This experiment using solid dispersion and mangiferin inclusion technique(MGF)was modified by differential scanning calorimetry(DSC),X ray diffraction(XRD)and Fu Liye(FT-IR MGF)on the infrared spectra of solid dispersion and package characterization of complexes,comparative analysis found that the molecular characteristics of mangiferin the peak of MGF solid dispersions and the inclusion of the change that mangiferin crystal structure changed,uniformly dispersed in the materials,the formation of amorphous structure,MGF-PVP,MGF-PEG,MGF-CD and MGF-Hp-CD beta beta preparation.(2)MGF solid dispersion and inclusion significantly improved in water solubility,the dissolution rate of mangiferin were MGF than raw materials,prepared into solid dispersion and inclusion complex of solubility and dissolution and improve the oil-water distribution coefficient,the more hydrophilic,mangiferin in water solubility and dissolution of the big.MGF solid dispersion and inclusion significantly improved in water solubility,the dissolution rate of mangiferin were improved compared with raw materials,new technology of mangiferin preparation(MGF)solubility and dissolution and improve the oil-water distribution coefficient,the more hydrophilic,mangiferin in water solubility and dissolution rate increases.(3)The raw materials are easy to be mangiferin in vitro intestinal flora metabolism,MGF by the new preparation technology of inclusion or solid dispersion treatment,MGF metabolic rate decreased,the performance of MGF-PVP solid dispersions of anti human intestinal flora metabolism than MGF-Hp-beta CD,MGF-PVP metabolic rate of solid dispersions of the slow decrease of mangiferin in the metabolic rate of the intestinal flora in the human body,the intestinal absorption of mangiferin to prototype drugs,improve the bioavailability of MGF,in order to obtain a more ideal effect.(4)When MGF was made into PVP solid dispersion,the bioavailability of MGF in rats could be significantly increased.