title: Supercritical fluid assisted atomization introduced by an enhanced mixer for micronization of lysozyme: Particle morphology, size and protein stability.
abstract: Supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM) was used to produce lysozyme microparticles with controlled particle size distribution in the range for aerosol drug delivery. The process is based on the atomization effect of carbon dioxide. The solubilization of certain amount of carbon dioxide in the solution plays the key role and the HCM can intensify mass transfer between carbon dioxide and liquid feedstock greatly. Water was used as the solvent to solubilize lysozyme and thus no organic residual was detected. The influences of process parameters on particle formation were investigated including temperature in the precipitator, pressure and temperature in the mixer, concentration of the solution and feed ratio CO(2)/solution. The particles were characterized with respect to their morphologies and particle size: well defined, spherical and separated particles with diameters ranging between 0.2 and 5μm could be always produced at optimum operating conditions. Bio-activity assay showed that good activity maintenance of higher than 85% for lysozyme was usually achieved. Solid state characterizations were further performed to investigate the changes of lysozyme in the process. Fourier transform infrared spectroscopy indicated that no change in secondary structure had occurred for processed lysozyme. X-ray diffraction analysis showed that the lysozyme particles produced remained similarly amorphous as the raw material. Differential scanning calorimetry and thermogravimetry analysis revealed that there was no significant difference in water association but with the increase of water content after processing.
authors: Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Zhe
authors: Z
authors: Du
authors: Yi-Xin
authors: YX
authors: Guan
authors: Shan-Jing
authors: SJ
authors: Yao
authors: Zi-Qiang
authors: ZQ
authors: Zhu
mesh_terms: D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D000431:Ethanol / Q000737:chemistry; D008837:Micrococcus / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D033362:Powder Diffraction; D011312:Pressure; D055550:Protein Stability; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D012997:Solvents; D014867:Water; D002245:Carbon Dioxide; D000431:Ethanol; D009113:Muramidase