Cyclodextrin Supramolecular Delivery System Improves The Stability Of Vitamin A Palmitate

Vitamin A,a fat-soluble micronutrient critical for many biological processes,is presented in all living organisms.The term of vitamin A refers to a group of substances with similar molecular structures,and principal and major biologically active substance is all-trans retinol,generally in the form of esters such as the acetate,propionate and palmitate.Vitamin A palmitate(VAP)is a widely used derivative of vitamin A which can not be produced by human body and has to be ingested with food or products of food supplements.Owing to multiple conjugated double bonds and ester,chemical properties of VAP are active that many factors such as heat,light,oxygen,humidity,acid and alkali can bring its oxidation,dehydration,hydrolysis and polymerization.Therefore,the technologies of emulsification and embedding are usually used to isolate vitamin A and its derivatives from light and oxygen to improve its stability.Currently,commercially available vitamin A preparations generally contain surfactants and antioxidants which can not be stored for a long time.Therefore,it is important to ameliorate the production process and using effect of VAP by exploring a simple technique to improve its stability.This thesis uses cyclodextrin metal organic frameworks(CD-MOFs)with a special high porosity structure as the carrier to integrate VAP to improve the stability of VAP.The main contents are as follows:High performance liquid chromatography(HPLC)was used to quantify VAP and and its preparations.Quantitative methods of VAP and CD-MOFs-VAP compounds were established.The effects of acid,alkali,heat,light and oxygen on VAP were investigated and the relevant substances were determined.The results revealed that VAP and its degradation products could be successfully separated under the established conditions of HPLC.Of all the factors,the acid,alkali and temperature had the most impact on the stability of VAP,and oxygen was second,and light had the least impact on its stability.Different types of CD-MOFs were prepared by solvothermal method andcharacterized by Scanning Electron Microscope(SEM),Fourier Transform Infrared Spectroscopy(FT-IR),Power X-ray diffraction(PXRD)and gas adsorption.The results of SEM,PXRD and gas adsorption indicated that different types of CD-MOFs were cubic crystal and highly porous materials with the uniform particle size.FT-IR results showed that coordination bonds between K+ and ?-CD in CD-MOFs.In addition,KOH-CD-MOFs neutralized with glacial acetic acid,namely neutralized CD-MOFs were chosen as carrier to load VAP with heating and refluxing,and the drug loading process was optimized.SEM,PXRD,FT-IR and gas adsorption were used to characterize neutralized CD-MOFs before and after loading VAP.The optimal drug loading process was that 200 mg of neutralized CD-MOFs suspended in 2 mL of 40mg/mL VAP ethanol solution with heating and refluxing(40 oC,400 rpm)for 120 min.Drug loadings of micron and nanometer neutralized CD-MOFs were about 10 % and14 %,respectively.The morphology and particle size of CD-MOFs before and after being neutralized with glacial acetic acid and the loading of VAP didn't change the appearance of the particles.The results of FT-IR and gas adsorption indicated that VAP was not only adsorbed onto the surface of neutralized CD-MOFs but also encapsulated into the cavities of neutralized CD-MOFs.Cross-linked CD-MOFs were prepared and combined with spray-drying method to prepare cross-linked CD-MOFs-VAP microcapsules.The stability of different types of CD-MOFs-VAP,cross-linked CD-MOFs-VAP microcapsules and vitamin A powder at60 oC were contrastively investigated.The optimized carriers for the protection of VAP stability were neutralized CD-MOFs from KOH-CD-MOFs and K2CO3-CD-MOFs.The stability of neutralized CD-MOFs-VAP and BASF Vitamin A powder were also investigated at 40 o C and 75 % relative humidity.In addition,drug-loading mechanism of VAP to CD-MOFs was analyzed by molecular simulation.The results indicated that the protective effects of different types of CD-MOFs on VAP were different,as follows:neutralized CD-MOFs > cross-linked CD-MOFs ? vitamin A powder > potassium tartrate CD-MOFs.Spray drying can be used to prepare CD-MOFs-VAP microcapsules,but it was less stable than cross-linked CD-MOFs-VAP due to the presence of water.For CD-MOFs-VAP compounds,VAP tended to stay in the middle of ?-CD pair in CD-MOFs.In conclusion,CD-MOFs were cubic crystals prepared with ?-CD as organic linkers and K+ as inorganic metal.Its crystallinity,porosity and relative rigidity of structure can be used as potential drug carriers for improving the stability of VAP.Fourthermore,it is not only beneficial to ensure precise dosing,less cost and food fortification of vitamin A,but also provides a new formulation trategy for improving the stability of drugs.