Synthesis Of Calcium Carbonate Microspheres And Study On Drug Release Properties

In this paper,the calcium carbonate hollow microspheres and porous vaterite calcium carbonate microspheres were synthesized by the complex decomposition method of aqueous solutions sodium carbonate(Na2CO3)and calcium chloride(CaCl2)in the presence of poly(acrylic acid)(PAA)?sodium dodecyl sulfonate(SDS)or sodium dodecyl benzene sulfonate(SDBS).We investigated carefully the changes of polymorphs?morphology and structure of the two kinds of calcium carbonate microspheres in the crystallization process according to the interaction relationship between Ca2+ and PAA,SDS or SDBS,creatively put forward the formation mechanism of calcium carbonate hollow microspheres and porous vaterite calcium carbonate microspheres.Through studying the main parameters which affected the morphologies and polymorphs of calcium carbonate microspheres,we obtained the optimum technological conditions for preparing the two kinds of calcium carbonate microspheres.Finally,we used the two kinds of calcium carbonate microspheres with different morphologies and polymorphs as drug carriers,Ibuprofen(IBU)was used as a model drug to compare their drug loading and sustained drug release in simulated gastric fluid(pH = 1.2)and simulated intestinal fluid(pH = 7.4).The main research results are as follows:1.In the double decomposition precipitation reaction system,because the electrostatic interaction of PAA and Ca2+ is stronger than that of SDS,the PAA chains would give priority to gather a large number of Ca2+ in the crystal growth process of calcium carbonate microspheres,according to the Gibbs-Thomson equation and the Fick's first law,we proposed the formation mechanism of calcium carbonate hollow microspheres.It was found that PAA and SDS had a great influence on the morphology and aggregation behavior of calcium carbonate hollow microspheres in the crystal growth process,too much or too little of the PAA and SDS concentration could not obtain calcium carbonate hollow microspheres with uniform particle size distribution and good dispersibility.The optimum process conditions for reaction temperature was T = 80,the concentration of PAA was 0.5 g/L,the concentration of SDS was 10 mmol/L.2.When using PAA and SDBS as additives,we could prepare good monodisperse,narrow size distribution and high vaterite content of porous calcium carbonate microsphere by the complex decomposition method.The study found that SDBS could form PAA-SDBS supramolecular chain structure in PAA aqueous solution,and the supramolecular chain structure could be used as a template to induce the formation of vaterite calcium carbonate.By studying the effects of reaction temperature.PAA concentration and SDBS concentration on the morphologies and polymorphs of calcium carbonate,the results showed that the effect of reaction temperature and concentration of PAA concentration on the polymorph of vaterite calcium carbonate is very small,but had a great influence on the morphology of microspheres.At low temperature and low PAA concentration,mainly obtained calcite calcium carbonate,and vaterite calcium carbonate became the main part with the increase of temperature and PAA concentration,but there were many broken microspheres.We also found the SDBS concentration had a significant effect on the polymorph and morphology of calcium carbonate,there would make regular morphology vaterite calcium carbonate microspheres with the increase of SDBS concentration.3.We studied the surface area and pore size distribution of the two kinds of different morphologies and polymorphs of calcium carbonate microspheres,found that the porous vaterite calcium carbonate microspheres had high specific surface area and smaller pore diameter.Then using ibuprofen as the model drug,the two kinds of microspheres as drug carriers,the results showed that the drug loading of porous vaterite calcium carbonate microspheres could reach 100.6 mg/g,the drug loading of calcium carbonate hollow microspheres was 87.5 mg/g.In the simulated gastric juice,the loaded drug of the two kinds of microspheres released rapidly,however,the former is a good drug delivery capability than the latter in the simulated intestinal fluid,its release time could last for 48 h,and the drug release time of calcium carbonate hollow microspheres was 32 h.