Preparation And Biological Evaluation Of Curcumin Ultrafine Powder

Curcumin, a natural pigment, extracted from turmeric rhizome of the ginger family of plants, has a wide range of pharmacological activity such as antiviral, antibacterial, anti-tumor, anti-inflammatory, anti-oxidation. However, curcumin is insoluble in water, its aqueous solution is instable at neutral to alkaline conditions, because of its rapid metabolism and its bioavailability is limited. Therefore, it is necessary to increase the solubility of curcumin in water, improve its vitro dissolution rate. A lot of researchs has been carried out by scholars world-wide to give a variety of new formulations of curcumin, particle size reduction is one of the significant technical means to achieve the above aim.In this paper, curcumin ultrafine powder were prepared by the high homogenization and supercritical anti-solvent process technology, preparation process of curcumin ultrafine powder was optimized:The physicochemical properties, chemical structure and dissolution of curcumin ultrafine powder were investigated The antitumor activity of curcumin ultrafine powder was tested.(1) Curcumin content analysis methods was establishedHPLC was used to analysis curcumin content. Methodological study results showed that curcumin had a good linear relationship in the concentration range 1-60 μg/mL. And within-day precision, between-day precision, stability, and recoveries were corresponded to technology requirement.(2) Curcumin ultrafine powder were prepared by the high homogenization technologyCurcumin ultrafine powderwere prepared by the high homogenization technology, and preparation process of curcumin ultrafine powder (power A)was optimized. The results showed that the mean particle size of curcumin nanosuspensions were (171.0±8.56)nm, and the PI was (0.6940±0.05). The optimized formulation was as follows:mannitol concentration 4%(W/W), pre-freezing temperatures -20℃, pre-freezing time 24 h. UV, IR, XRD and HPLC showed that chemical structure of curcumin ultrafine powder was not obviously changed; and the solubility of curcumin ultrafine powder in water substantially increased.Compared with curcumin powder, the dissolution velocity of curcumin ultrafine powder were significantly improved, and the dissolution was 80% at 120 min. The high pressure homogenization technology employed can be successfully used to prepare curcumin ultrafine powder.(3) Curcumin ultrafine powder were prepared by the supercritical anti-solvent technologySupercritical anti-solvent (SAS) process is taken to prepare the curcumin ultrafine powder(powder B), with acetone as solvent, the size of micro particles as quality indexes. Precipitation pressure, concentration of solution, drag solution on flow rate, precipitation temperature were studed. The optimized technological conditions obtained were as followed:precipitation pressure:30 Mpa, concentration of solution:12.5 mg/mL, drag solution on flow rate:9 mL/min, precipitation temperature:53℃, the mean particle size of curcumin powder were 450-550 nm. IR, UV showed that chemical structure of curcumin ultrafine powder was not obviously changed; XRD showed that the crystallinity of curcumin ultrafine powder was much lower than curcumin powder, the lower the the crystallinity; the better the the water-soluble. TG/DTG、DSC showed that compared with curcumin powder, the stabiliy of curcumin ultrafine powder was not changed much and its melting point was much lower. Water-soluble experiments showed that the solubility would increase while the particle size decreased.(4) Anti-tumor activity of curcumin ultrafine powder in vitro was testedThe inhibitory effect of curcumin ultrafine powder on HepG2, HCT116 cells were investigated by MTT method. The results showed that both cell growth was significantly inhibited, the inhibitory became stronger. when the concentration of curcumin ultrafine powder was increased. The IC50 on HepG2 cells were 11.95 μg/mL(powder A)% 12.76 μg/mL (powder B) and 24.14μg/mL(curcumin powder) respectively. The IC50 on HCT116 cells were 10.87μg/mL(powder A)、11.24 μg/mL(powder B) and 24.14 p.g/mL(curcumin powder). Therefor, the anti-tumor activity in vitro was enhanced and its bioavailabilitywas further improved by reducing the particle size of curcumin.