Preparation Of High Water Soluble Lutein Solid Dispersion

Lutein,a natural pigment widely found in nature,has several efficacies such as antioxidant property,anti-cancer property,prevention of cardiovascular diseases,prevention of retinopathy,cardiovascular protection and anti-atherosclerosis.However,the special chemical structure of lutein itself makes it low in solubility,poor in stability and easy to be decomposed under light and acid conditions,which limits its application in food industry.In this work,lutein solid dispersion was prepared from lutein by solid dispersion technology,which could significantly improve the water solubility,stability and bioavailability of lutein.The main research contents and results are as follows:?1?Lutein solid dispersions were prepared with water-soluble carriers such as polyethylene glycol 2000?PEG2000?,polyethylene glycol 4000?PEG4000?,polyethylene glycol 6000?PEG6000?,poloxamer 188?P188?,poloxamer 407?P407?,?-cyclodextrin??-CD?,?-cyclodextrin??-CD?,?-cyclodextrin??-CD?,HP-cyclodextrin?HP-?-CD?and polyvinylpyrroli-done K₃₀(PVPK₃₀).The optimum preparation method and single carrier were selected by using dissolution and solubility as the evaluation indexes.Results showed that the lutein solid dispersion prepared by solvent method with PVPK₃₀ as water-soluble carrier had the best dissolution effect.Through single factor experiments and orthogonal experiments,the optimal conditions were deteminded:?ratio of drug to carrier,1:25;preparation temperature,60?;ethanol dosage,30 mL;dissolution speed,75 r/min?.The lutein-PVPK₃₀ solid dispersion prepared under these conditions had a total dissolution rate of 84.26%in 60 min and a high solubility of 90.23?g/mL.The lutein-PVPK₃₀ solid dispersion was then characterized by fourier transform infrared spectroscopy?FTIR?,differential scanning calorimetry?DSC?,scanning electron microscope?SEM?and X-ray diffraction?XRD?.Results showed that the lutein presented an amorphous state in lutein-PVPK₃₀ solid dispersion and formed hydrogen bond with PVPK₃₀ carriers.The stability of lutein-PVPK₃₀ solid dispersion was investigated and results indicated that the dissolutions under high temperature?60??,high humidity?75%RH?and strong light?4500±500 LX?,respectively for 10 days were still remained at 79.54±0.28%,76.46±0.43%and 66.26±0.62%,illustrating that the stability was significantly improved.The solubility of lutein-PVPK₃₀ solid dispersion was compared with that of lutein products domestic and overseas and results indicated that the prepared lutein-PVPK₃₀ solid dispersion had remarkable solubilizing effect.?2?Multi-solid dispersions were prepared with the combination of carriers including PVPK30,PEG6000,P407,polyethylene caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer?Soluplus?hydroxypropyl methyl cellulose?HPMC?,vitamin E-polyethylene glycol-succinic acid ester?TPGS?on the basis of single carrier preparation process.The ratio between carriers was 1:1 and the ratio between lutein and the combined carriers was 1:25.The dissolution and solubility were used as the evaluation indexes and results indicated that the multi-solid dispersion prepared by PEG6000,P188 and TPGS had better dissolution effect.The optimal proportion of PEG6000,P188 and TPGS was optimized as PEG6000:P188:TPGS=44.461:33.101:22.258 through Design-Expert 8.0.At this ratio,the solid dispersion prepared by the melting method had a total dissolution rate of 85.59%in 30min and a high solubility of 106.80?g/mL,which was significantly higher than that of the raw material lutein.The multi-solid dispersion was also characterized by FTIR,SEM and XRD and results indicated that the lutein existed in solid dispersion in amorphous or cryogenic form.The stability of the prepared multi-solid dispersion was investigated and results indicated that the dissolutions under high temperature?60??,high humidity?75%RH?and strong light?4500±500 LX?,respectively for 10 days were still remained at 72.60±0.56%,70.21±0.46%and56.25±0.58%,illustrating that the stability was also significantly improved.The solubility of the prepared multi-solid dispersion was also compared with that of lutein products domestic and overseas and results indicated that the prepared multi-solid dispersion had remarkable solubilizing effect.?3?The bioavailability of lutein solid dispersions in rats was investigated.Pharmacokinetic analysis software was used to analyze the data and calculate the pharmacokinetic parameters.Results indicated that the peak concentrations(C_max)of lutein bulk drug,lutein-PVPK₃₀ solid dispersion and lutein multi-solid dispersion were 1.840?g/mL,1.148?g/mL and 1.044?g/mL,respectively;the peak times(T_max)of them were 2 h,6 h and 6 h,respectively;the elimination half-life(t_1/2)were 4.250 h.15.220 h and 16.250 h,respectively;the area under the curve of the drug were?AUC?were 8.856?g?h/mL,17.208?g?h/mL and 15.603?g?h/mL,respectively.Meanwhile,the relative bioavailability of the two prepared solid dispersions was 194.31%and176.19%,respectively.It indicated that the solid dispersion was completely released in the intestine and had a good sustained release effect in body.