Study On The Preparation And Application Of Iron Threonate And Its Nanoliposomes

Iron is one of the essential trace elements in living organisms and plays an important role in maintaining physiological activities of the body.Poor diet and special physiological conditions may induce iron deficiency in the body,and then develop into iron deficiency anemia.Oral iron supplementation is the main way of iron supplementation in clinic,which can improve the body iron nutritional status,correct iron deficiency anemia.Chelated iron of amino acid is an excellent iron supplement,which has better patient compliance and bioavailability than inorganic iron salt.The iron supplement tablets developed from chelated iron of amino acid have many advantages such as accurate dose,stable quality,convenient use and obvious effect.In this paper,iron threoninate was synthesized by direct synthesis with water system,using threonine and ferrous sulfate as raw materials,and the product was analyzed by infrared spectroscopy analysis and X-ray diffraction analysis to characterize the iron threoninate.The results showed that the prepared iron threoninate was chelate,the content of ferrous iron and total iron were 11.37% and12.49%,respectively,and the ratio of ferrous iron to total iron was 91.03%.Using the orthogonal test method and the encapsulation rate and particle size as the evaluation indexes,the cholesterol dosage,core material load and tween 80 dosage in the preparation process of iron threoninate nano-liposomes were optimized.And the effects of different ultrasonic powers on the encapsulation rate and particle size of nano-liposomes were studied.The results showed that appropriate ultrasonic power(250 W)was helpful to improve the encapsulation rate and reduce the size of nano-particles.When the concentration of egg yolk lecithin was fixed at 15 mg/mL,the nano-liposomes prepared at the proportion of egg yolk lecithin: cholesterol: iron threonine: tween 80=1:0.1:0.2:0.6 had good quality,the encapsulation rate was 77.3%,the average particle size was 87.42 nm,the PDI was 0.308,the average Zeta potential was-44.7mV,the appearance was uniform and the property was stable.The stability of iron threoninate and ferrous sulfate under different storage conditions was compared,and the results showed that the stability of iron threoninatein solid or solution was better than that of ferrous sulfate.Compared with in pH=4and in pH=6,the oxidation stability and hydrolysis stability of iron threoninate solution were higher in pH=5.The study on the effects of different factors(temperature,pH)on iron threoninate nano-liposome stability showed that overly acidic and high temperature were not conducive to the stability of liposomes,and the low storage temperature(4?)and close to neutral(pH = 6.8)storage conditions were good for the stability of iron threoninate nano-liposome.With iron threoninate as the main drug,the interaction between the main drug and the excipient was studied to verify the reliability of the selected excipient.Using the orthogonal test method and the hardness and dissolution as the evaluation indexes,the proportion of the selected excipient was optimized,and the optimal schemes were obtained as follows: iron threoninate 40.4%,microcrystalline cellulose 40.4%,polyvinylpyrrolidone 6.31%,coprovidone 10.1%,magnesium stearate 0.76%,silicon dioxide 0.51% and vitamin C 1.52%.Iron threoninate tablets were prepared by direct powder compression.According to the tablet inspection standards in "Chinese pharmacopoeia" version 2015,the quality of iron threoninate tablets was inspected,and the rationality of the preparation technology was evaluated.The results showed that the prepared tablets had uniform color,smooth and complete surface,consistent thickness,average tablet weight of about 198 mg,average ferrous content of about 8.9mg/ tablet,average hardness of about 75 N,maximum disintegration time of about 13 min,dissolution amount of about 100% at 25 min.