Study On Synthesis Of Stable Amorphous Nano-sized Calcium Carbonate Assisted By Polyvinylpyrrolidone And It’s Drug-loading Properties

Calcium carbonate is widely distributed in nature.It is both a geological mineral and a rich store of carbon dioxide.It is also a biological component of the shell of mollusks and is the main component of the cuticles of crustaceans and protozoan bones.Now found that there are three amorphous forms of calcium carbonate（calcite,aragonite and vaterite,with decreasing stability in turn）,three metastable forms of hydration（Calcite monohydrate;hexahydrate calcium carbonate and hemihydrate calcium carbonate）,and an extremely unstable amorphous nano-calcium carbonate（ACC）phase.Compared with other calcium carbonate,ACC has the advantages of small particle size,large specific surface area and high solubility.However,it is also highly unstable and can be easily converted to aragonite or calcite under different conditions.At present,ACC exists stably in nature only in organisms such as sea urchin crayfish,coral and gastropods.As a temporary storage phase of calcium ions,it is very important to control the synthesis of stable ACC.CO₂ and Ca（OH）₂ were used as raw materials to synthesize ACC in methanol medium,and the effect of reaction time of CO₂ pressure,temperature and rotation speed on ACC yield was investigated.At the same time,the crystallization behavior of ACC nanoparticles in methanol-water system was studied.Then,amorphous nano-sized calcium carbonate-polyvinylpyrrolidone（ACC-PVP）particles with high stability were prepared using polyvinylpyrrolidone（PVP）as stabilizer.The effects of different PVP additions on the specific surface area and stability of ACC were investigated.The crystallization behavior of ACC,ACC-PVP particles and ACC in methanol-water were characterized by Fourier transform infrared spectroscopy（FT-IR）,X-ray diffraction（XRD）transmission electron microscopy（TEM）,field emission scanning electron microscopy（FE-SEM）thermogravimetric and differential thermal analysis（TG-DSC）.Using 5-fluorouracil（5-FU）and curcumin（CUR）as model drugs,the performance of ACC-PVP as drug carrier was studied,and the dissolution performance of composite particles was investigated by in vitro dissolution test.Research shows that:In the process of ACC synthesis experiment,when the CO₂pressure was 0.4 MPa,the temperature was 50℃,the rotation speed was 600 r·min^-1,and the reaction time was 1h,the ACC with a yield of 74.02%was obtained,and the specific surface area was as high as 344 m²·g^-1.The high specific surface area was an important factor as a drug carrier.As the water content of the solution increases,ACC nanoparticles in the methanol-water system will be transformed into metastable vaterite and then into calcite which is more thermodynamically stable.When the water content is 18%,a highly monodisperse calcite is obtained.Using polyvinylpyrrolidone（PVP）as stabilizer,highly stable amorphous nano-calcium carbonate-polyvinylpyrrolidone（ACC-PVP）particles were prepared.The particles can be stable for 8 months without crystallization.With the increase of PVP content,the specific surface area of ACC-PVP particles decreased,which may be caused by the adsorption of PVP into the pores of ACC particles.5-Fluorouracil（5-FU）and curcumin（CUR）were used as model drugs,and the dissolution properties of the composite particles were investigated by in vitro dissolution tests.The results showed that 5-FU@ACC-PVP granule showed good p H responsiveness,and Partial granule showed good drug release in simulated gastric juice environment.The multi-pore ACC-PVP granule could be used as a drug delivery carrier for p H-responsive and insoluble drugs.