Preparation Of Uniform Beclomethasone Dipropionate Nanoparticles And Its Solubility Using Subcritical Water

It has been reported that the vast majority of drugs in pharmaceutical are poorly-water soluble with low absorption and bioavailability. The poorly-water soluble drugs are limited due to their poor water-solubility and low dissolution rate in clinic applications. To solve this problem, many research works have been done to find that the presence of fine particles increase the dissolution rate. Therefore, the preparation of the drugs with narrow particle size distribution is necessary to develop the solubility of the drug. The media milling is a common way to produce nanoparticles. However, this process is often limited by the high energy input, drugs contamination and poor control of particle size. Compared with the conventional preparation processes, SBCW process has been used extensively for processing nanoparticles with non-toxic. SBCW is hot water under pressure to maintain liquid phase and non-polar organics solvents are miscible in these phases. As the water temperature is increased, the polarity of water begins to change and subcritical water has the property of dissolving non-polar organic. In our report, we have studied the solubility of beclomethasone dipropionate (BDP) in SBCW; established the thermodynamic model after collected the solubility data; prepared BDP nanoparticles using the SBCW technique.First, we investigate the effect of equilibrium time on the solubility of BDP in SBCW. The result presented that the equilibrium time tended to be longer when the SBCW temperature was increased from 120℃ to 160℃. Minimum equilibration time of 20 min was selected. Secondly, the effects of pressure on the BDP solubility in SBCW were explored. It can be concluded that the effect of pressure on solubility in subcritical water remains insignificant when the range of pressure from 6MPa to 8MPa. In the end, we also investigate the solubility of BDP in SBCW system at different temperature and the volume fraction of ethanol. The result showed that when the temperature measurements was extended from 120 to 180 ℃, the solubility of BDP was found to increase, especially dramatic increase in solubility over 150℃. The addition of ethanol into the SBCW system led to the solubility of BDP in SBCW increased up to 10 times.The preparation process of nanoparticles from BDP used the SBCW technique. Fine particle morphology will be obtained when we change the anti-solvent temperature, the SBCW temperature, volume ratios of solvent to anti-solvent, different surfactant types and dosage. BDP particle sizes below 60 nanometers are produced applying the SBCW under the optimal experiment conditions which were:anti-solvent temperature 0℃, SBCW temperature 140℃,the ratio SBCW to water 1/3, PEG and PVP as surfactant, content of surfactant 0.018%. FT-IR analysis results suggested that the molecular structures of the raw and processed BDP had no change. XRD analysis showed that the BDP nanoparticles exhibited the lower peak intensities, with is due to the SBCW process resulting in the formation of the lower crystallinity and the smaller particle size of BDP. The dissolution rates with BDP nanoparticles displayed more effective than the raw drug. After 120 min, approximately 60.13% of the BDP nanoparticles dissolved, respectively, while only 10.78% of the raw drug dissolved.