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Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to prepare micrometric particles of a labile protein, i.e. , trypsin from aqueous solution without use of any organic solvents. The trypsin particles precipitated had various morphologies under different process conditions, with particle diameters ranging from 0.2 to 4 μm. FTIR, SDS-PAGE, CD and fluorescence spectra were performed to analyze the structural stability of the protein, and trypsin retained above 70% of the biological activity. Besides, chitosan was selected as the polymer carrier in an effort to prepare trypsin composite microparticles via SAA-HCM process. The influences of chitosan molecular weight, polymer/protein ratio and solution concentration on the particle morphology and size distribution were investigated in detail. Non-coalescing spherical composite microparticles with a narrow particle distribution (0.2–3 μm) could be obtained. The SAA-HCM prepared particles were amorphous as demonstrated by XRD and had a loading efficiency about 90%. The protein release profiles of the composite microparticles were evaluated using both the immersion condition and a Franz diffusion cell. Finally, the distribution of the protein within the particles was characterized through CLSM analysis of FITC-labeled trypsin-loaded chitosan microparticles. The SAA-HCM process is demonstrated to be a protein-friendly and promising technique for production of protein and polymer/protein composite particles formulations from aqueous solutions for drug delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to prepare bovine serum albumin (BSA) microparticles. Water was used as the sole solvent. A hydrodynamic cavitation mixer was applied to improve mass transfer and achieve a continuous near-thermodynamic-equilibrium solubilization of SC-CO2 in the liquid solution. Under the different conditions, the prepared BSA microparticles had various morphologies, such as corrugated particles, smooth hollow spherical particles and cup particles, with particle diameters ranging from 0.3 to 5μm. The microparticle formation process was elucidated with the shell formation and central bubble mechanism. Compared to native BSA, BSA microparticles did not show significant change in primary structure, according to the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The secondary structure of BSA was characterized by Fourier transform infrared spectroscopy (FT-IR). No new peaks were observed after SAA-HCM processing. In addition, the crystalline structure of the BSA microparticles was demonstrated to be amorphous because of the sudden supersaturation in the precipitation process. The SAA-HCM process is expected to be a promising technique for producing microparticles suitable for pulmonary delivery of therapeutic macromolecules. [ABSTRACT FROM AUTHOR]

Abstract: A novel micronization technique so-called supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM) was used to produce the sodium cellulose sulfate (NaCS) microparticles with well-defined spherical morphologies and controlled particle size distributions in aqueous solution. The process parameters such as mixer temperature and pressure, the mass flow ratio, precipitator temperature, solution concentration and the molecular weight of NaCS were investigated in detail to evaluate their influences on the morphologies and size distributions of precipitates. Spherical NaCS particles with mean diameters ranging from 0.3 to 3.0μm were produced at the optimum operating conditions and narrow particle size distributions were obtained. It is natural to put forward the particle formation mechanism of deflated balloons. Compared with the unprocessed NaCS, there was no significant change on the primary structure and stability of the NaCS processed by SAA-HCM verified by Fourier transform infrared spectroscopy. The X-ray diffraction and thermo-gravimetric analysis were also used to investigate NaCS modifications and a slight change in crystalline state with higher thermal stability was observed when treated by SAA-HCM process. The results indicated that NaCS micronization by SAA-HCM process was expected to be a promising technique for drug delivery system. [Copyright &y& Elsevier]

Abstract: A hydrodynamic cavitation mixer (HCM) was introduced in the supercritical fluid assisted atomization (SAA) process to improve mass transfer. SAA-HCM resulted in a more homogenous primary droplet and, as a consequence, narrower particle size distributions. Levofloxacin hydrochloride (LH) being selected as a model drug, the effects of cavitation generator on morphology, size, and distribution of precipitated particles were evaluated. In addition, the influences of several process parameters, such as the feed ratio between CO2 and liquid solution, solute concentration, etc., were investigated in detail. Spherical amorphous micron-sized particles were obtained at different CO2-solution feed ratio and solute concentrations. In all cases, particles with diameters smaller than 2.1μm were produced. The SAA-HCM is expected to be a promising technique for producing microparticles suitable for pulmonary delivery in drug delivery applications. [Copyright &y& Elsevier]

Abstract: Supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM) was used to prepare chitosan microparticles with the well-defined spherical morphology and the controlled particle size distribution as a promising carrier for drug delivery system. Chitosan with different molecular weights (3kDa, 50kDa, 300kDa) was successfully micronized, in which water was used as the solvent for 3kDa chitosan, while 1.0% (v/v) acetic acid aqueous solution was used for 50kDa and 300kDa chitosan, respectively. The process parameters including operating pressure and temperature in the mixer, mass flow ratio of CO2/solution, precipitator temperature and solution concentration were explored to evaluate their influences on the morphologies and size distributions of precipitated particles. Results showed that particle size tailoring (ranging between 0.2 and 5μm) could be achieved through modulation of the process parameters. After processing by SAA-HCM, Fourier transform infrared spectroscopy did not indicate significant change in the main structure of chitosan microparticles. Compared with raw materials, a decrease in crystallinity and thermal stability was observed for the SAA-HCM processed chitosan microparticles, as demonstrated by X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. [Copyright &y& Elsevier]