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Zhao et al Dovepress increase their surface area, thus enhancing the solubility and dissolution rate of these drugs.18 Recently, the wet- milling technique, a type of mechanical communication process, was used to prepare the curcumin nanoparticles of size ranging from 2 to 40 nm.2 However, mechanical communication does not represent the ideal micronization process since both the properties of the compound and the surface properties of the particles might be altered in an uncontrolled manner. Flash nanoprecipitation from a coarse oil-in-water emulsion was developed to fabricate the curcumin nanoparticles with a mean size of about 40 nm.19 In this process, spray-drying was employed to obtain fine curcumin powders. However, this method may suffer from the residual organic solvent and surfactants. Furthermore, spray-drying requires high temperatures and may induce denaturation of active substances. was designed to systematically investigate the actual effects of the processing parameters, including the flow rate of curcumin solution, precipitation pressure, concentration of curcumin solution, and precipitation temperature, on par- ticle size. Fourier transform infrared (FTIR) spectroscopy measurement, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermogravimetric (TG) analysis were used to study the chemical and physical properties of the nanoparticles fabricated using the SEDS process. Furthermore, the solubility and dissolution rate of curcumin were also measured to evaluate its pharmaceuti- cal performance. Materials and methods Materials Curcumin was purchased from International Laboratory (USA). CO2 with a purity of 99.9% was supplied by Hong Kong Specialty Gases Co., Ltd. (Hong Kong). The solvent, acetone, was purchased from Advanced Technology & Industrial Co., Ltd. (Hong Kong). All other compounds were of analytical purity. Preparation of curcumin nanoparticles by the seDs process The experimental apparatus of the SEDS process consists of three major sections: a CO2 supply system, an organic solution delivery system, and a high-pressure vessel. The schematic diagram of the SEDS process is shown in Figure 1. In this process, when the desired experimental conditions were reached, curcumin dissolved in acetone was injected into the high-pressure vessel via a stainless steel coaxial nozzle simultaneously with scCO2 using a high performance liquid chromatography pump. After all the solution was deliv- ered into the high-pressure vessel, fresh CO2 was pumped to wash precipitated particles for about 30 minutes to eliminate any residual organic solvent. During the washing process, the precipitation temperature and pressure were maintained as described above. After the washing process, the CO2 flow was stopped and the CO2 in the high-pressure vessel was slowly depressurized to atmospheric pressure. The curcumin nanoparticles were then collected on the filter at the bottom of the high-pressure vessel for characterization. Full factorial designs (FFD) To investigate the influence and significance of the four process parameters (the flow rate of curcumin solution, precipitation pressure, concentration of curcumin solution and precipitation temperature) in the SEDS process on both the morphology and particle size of curcumin nanoparticles, International Journal of Nanomedicine 2015:10 Recently, supercritical carbon dioxide (CO2) (scCO2) technologies have shown great potential in the field of par- ticle formation, especially drug micronization.20 The scCO 2 technologies present many advantages, including low critical conditions (Tc =304.1 K, Pc =7.38 MPa), few or no solvent residue, non-flammability, low cost, and being environmen- tally benign.21 So far, the most commonly used technique for particle formation using scCO2 is the supercritical antisolvent (SAS) process, in which scCO2 is used as an antisolvent for the precipitation of drugs dissolved in organic solvents. In the SAS process, an organic solution containing the solute is sprayed via a nozzle to a high-pressure vessel with scCO2, resulting in the formation of a complete mixture of the organic solution and scCO2. Continuous feeding of scCO2 induces the supersaturation of active substances. Finally, particles can be precipitated in the vessel. Solution-enhanced dispersion by scCO2 (SEDS) is a modified SAS process. In this process, a solution containing the solute and scCO2 are atomized via a specially designed coaxial nozzle to obtain droplets of small size and enhance mixing to increase mass transfer rates. In addition to acting as an antisol- vent, scCO2 is used as a “dispersing agent” to improve mass transfer between scCO2 and droplets. Therefore, very small particles can be produced.22 Particle size distribution and mor- phology of the solute can also be controlled by adjusting the parameters of the SEDS process, including the concentration of the solute, flow rate of the solution, temperature, and pres- sure of scCO2. However, studies on the formation of curcumin nanoparticles by scCO2 technologies, especially the SEDS process, remain unreported, although scCO2 technologies offer great advantages for the formation of nanoparticles. In the present study, the SEDS process was used to prepare curcumin nanoparticles. A full factorial experiment 3172 submit your manuscript | www.dovepress.com DovepressPDF Image | curcumin nanoparticles via dispersion by supercritical cO2
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