Preparation And Evaluation Of Lutein Tablets Based On Solid Dispersion Technology

Lutein is a natural antioxidant extracted from marigold,which has many pharmacological effects such as protecting the eyes,preventing age-related macular degeneration(AMD),anti-cancer,anti-oxidation,anti-atherosclerosis and protecting cardiovascular.However,lutein is easily degraded under strong acidic conditions and with poor water solubility and stability,which results in low bioavailability and limiting its clinical application.In this paper,lutein was prepared into solid dispersion,then pressed and enteric-coated to prepare lutein solid dispersion enteric-coated tablets,which can improve its water-solubility and stability,reduce the destruction of gastric acid and improve the bioavailability.Lutein solid dispersion was prepared by solvent method.The best preparation conditions were obtained with dissolution rate as the index: the carrier was povidone k30,the ratio of drug to carrier was 1:20,the preparation temperature was 70°C,then the sample was dried in a vacuum drying oven at 45°C for 24 h.The cumulative dissolution rate of the solid dispersion reached 90.48% within 45 minutes.The characterization results showed that the lutein particles were uniformly dispersed in the povidone k30 in an amorphous state,and the lutein-povidone k30 solid dispersion was effectively formed.Hydrogen bonds were formed between them,which can block recrystallization of the drug,delay phase separation and then increase the stability of the solid dispersion.The lutein solid dispersion was sensitive to temperature,humidity,and light,therefore it should be stored in a dry environment and kept away from light and heat.Lutein solid dispersion tablets were prepared by powder direct compression method.The formulation conditions of lutein solid dispersion tablets were optimized by single factor test and star point design-effect surface method.The optimum prescription was as follows: the amount of solid dispersion was 44%,the proportion of mixed diluent(compressible starch: lactose)was 1.99:1 and the dosage was 49.32%,the amount of disintegrating agent(cross-linked polyvidone)was 3.28%,the amount of the cosolvent(sodium dodecyl sulfate)was 2.90%,and the amount of the lubricant(magnesium stearate)was 0.5%.The tablet exhibited uniform color,smooth surface and no defects,the weight difference,disintegration time and hardness were all meet the requirements of the Pharmacopoeia,and the cumulative dissolution rate reached 93.28% within 45 min.The lutein solid dispersion tablet was most sensitive to humidity and more sensitive to temperature and light,and it should be protected from light and moisture during storage.Lutein enteric-coated tablets were prepared by trundle pan coating method.Combined with the results of single factor test,the optimum formulation and technology conditions of lutein enteric-coated tablets were optimized by orthogonal test with release degree T and coating efficiency P as comprehensive evaluation index(Y).The optimum formulation and technology were as follows: the amount of enteric material(Eudragit L-100)was 6%,the amount of plasticizer(diethyl phthalate)was 25% of the amount of enteric material,and the amount of anti-adhesive(talc powder)was 40% of the amount of enteric material,the inlet air temperature was 30°C,the rotating speed was 30 r/min,the coating weight was up to 6%,and the heat treatment time was 4 hours.The cumulative release rate of lutein enteric-coated tablets was less than 5% in 2h in acidic medium and reached 87.52% in 1h in artificial intestinal fluid,with good batch reproducibility.Lutein enteric-coated tablets exhibited good stability and could be stored for a long time.The bioavailability of lutein solid dispersion tablets and enteric-coated tablets in rabbits was studied.The pharmacokinetics processes of lutein conventional tablets,solid dispersion tablets and enteric-coated tablets in rabbits were all consistent with the one-compartment model.The peak concentration of the three formulations were 6.63±1.40,23.51±1.29,and 16.84±1.35 ng/m L,respectively,the peak time were 2.47±0.14 h,2.55±0.04 h and 3.70±0.14 h,respectively,and the area under the concentration time curve were 66.54±8.07,210.63±18.55 and 274.18±9.86(ng/mL)*h,respectively.With the conventional tablets as reference preparation,the relative bioavailability of lutein solid dispersion tablets and enteric-coated tablets were 316.55% and 412.05% respectively,and the bioavailability of lutein was significantly improved.