| Sustained-release and controlled-release drug delivery systems are effective formulations to gain the maximal drug efficiency and to reform the method of taking drugs. Supercritical Fluid Deposition (SCFD) technology has been proved to be an effective way to load the drug particles in the nanoscale channels of mesoporous silica substrate. The influencing factors and mechanism of preparing nanocomposites, thermodynamics and kinetics behaviors of using SCFD method, drug release mechanism were investigated in this work. The main work and experimental results are as follows:(1) The solubility of ibuprofen in the carbon dioxide was tested through a high-pressure view cell. It can be as high as7.299×10-4to37.841×10-4at the temperature from25℃to47℃, pressure from7.2MPa to15.6MPa.. At a constant temperature, the solubility of IBU in scCO2increases with the increase of the pressure. The higher the temperature, the influence of pressure on the solubility was more obvious. Chrastil model, Mendez-Santiago-Teja model and the Solubility Parameter Model was used to correlate the measured solubility experimental data.(2) Deposition of ibuprofen into SBA-15was carried out to prepare controlled-release nanodrug using supercritical carbon dioxide (scCO2) as solvent at the pressure of8-24MPa, temperature of25-50℃, deposition time of6-48h, the precursor concentration of0.63-7.5g/L. The characteristic of the obtained materials was performed with X-Ray Diffractometry (XRD), Scanning Electron Microscope (SEM) and N2adsorption-desorption isotherms; the results indicate that most drugs adsorbed were inside the nano-scale channels.It was found that the drug loading increased with the increase drug concentration. The experiments were repeated; it showed better repeatability of IBU/SBA-15nanocomposite prepared using SCFD.(3) To compare with the nanodrug using SBA-15substrate, MCM-41was also used as a substrate. The drug loading was31.92%for MCM-41, and under the same conditions for SBA-15it was36.96%. This is because the pore diameter of SBA-15was larger than MCM-41. For the release of two kinds of substrate, the difference of balance time was great. The balance time of two samples are respectively5h and2h. The same conditions for MCM-41, two kinds of sample balance time is respectively50h and35h. The drug indicated a good sustained-release characteristic. (4) The adsorption isotherm of ibuprofen deposited on SBA-15was tested at37℃and17MPa. Langmuir, Modified Langmuir and Freundlich adsorption model were fitted with experimental data. By comparison of the three models, it showed that three model fitting error were all less than10%. Langmuir and Modified Langmuir were used to the experimental adsorption kinetics calculations. The kinetic investigation based on a mass differential equation showed that at17MPa,37℃and precursor concentration of0.017mol/m3, the equilibrium concentration of ibuprofen in supercritical carbon dioxide is about0.0105mmol/m3scCO2and equilibrium time is about35000s.(5) In vitro release experiments of ibuprofen/SBA-15were conducted. Several release models were used to model the release kinetics for all the samples and a good agreement was obtained between the model representation and experimental data. A certain trend of the release of ibuprofen/SBA-15prepared at different conditions was found. With the increase of precursor concentration, the loadings gradually increased, the drug release rate slowed down and the equilibrium time was also reduced. Pressure, time and temperature were not monotonic relationship with the loadings, the constant k and diffusion coefficient n, namly, the drug release and the equilibrium. |
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