Preparation Of Emodin-Calcium Carbonate Composite Particles By Supercritical Carbon Dioxide And Its Properties

Emodin is a natural compound,mainly derived from polygonaceae plant polygonum cuspidatum,rhubarb palm,cassia,polygonum multiflorum and aloe.It has a wide range of medicinal value and has a variety of biological activities,but emodin contains a large number of free phenolic hydroxyl groups,easily oxidized in the air,poor solubility,low bioavailability,especially when used as an anticancer drug,the powerful side effects brought by the systemic effect after administration have greatly affected its clinical treatment applications.Based on this,we prepared emodin-calcium carbonate composite particles in a one-step process with low cost,high safety,good biocompatibility,and p H-sensitive calcium carbonate as the carrier to improve the water solubility of emodin and bring it after systemic administration side effects.In this experiment,supercritical carbon dioxide carbonization method was used to synthesize porous vaterite calcium carbonate with ethanolamine?MEA?as the crystal form control agent and saturated calcium hydroxide as the calcium source.The optimal reaction conditions for the synthesis of calcium carbonate with drug loading capacity were explored.Then according to the central composite design,a four-factor five-level response surface analysis test is designed.The interaction effects of MEA concentration,operating pressure,operating temperature and reaction time on the calcium carbonate crystallization process were analyzed.Finally,based on the optimal reaction conditions,the model drug was added into to synthesize emodin-calcium carbonate composite particles,and the effect of the amount of emodin added on the composite particles was discussed.XRD,¹³C NMR,FT-IR,SEM,TG-DSC particle size analyzer and other characterization methods were used to investigate the reaction mechanism of the crystal morphology of calcium carbonate and emodin-calcium carbonate composite particles.The dissolution performance of the composite particles was investigated by in vitro dissolution experiment.The results showed that:in the process of calcium carbonate synthesis,pure calcite was prepared under the condition of low concentration MEA,while almost pure vaterite was prepared when the MEA content was 9.5 ml,and the content was as high as 92.46%.Through the results of 3D response surface analysis and analysis of variance,it is concluded that high MEA concentration,lower reaction temperature and shorter time are favorable for the formation of vaterite,and various reaction factors affect each other,such as the longer the time vaterite content is lower,but in the longer time under the condition of lower pressure instead of the content of vaterite is higher;¹³C NMR results indicate that MEA reacts with CO₂ to form carbamate ions at 164 ppm,which can be subsequently converted to bicarbonate by hydrolysis reaction and converted to carbonate in alkaline aqueous solution and reacts with Ca²⁺to produce calcium carbonate.Then the released MEA continues to absorb new CO₂,and 61.50 ppm and 43.33 ppm correspond to the two peaks of carbamate.The in vitro dissolution of the composite particles was analyzed in buffer solutions at p H 7.4 and 5.8.The results showed that the dissolution of the composite particles was significantly higher than that of the physical mixture and free emodin.XRD results proved that this was caused by the presence of emodin in the formed composite particles in an amorphous form in the vaterite mesoporous cavity.