Preparation of dextran glassy particles through freezing-induced phase separation

This report demonstrates a novel method to prepare fine polysaccharide glassy particles of uniform sizes under a condition without water/oil and water/air interfacial tension and cross-linking reagents. When a co-solution of dextran and polyethylene glycol (PEG) was frozen gradually, phase separation occurred during which dextran formed the dispersed phase and PEG remained in the continuous part. Fine dextran glassy particles were harvested after lyophilizing this frozen sample, followed by re-dissolving the continuous phase (PEG) in dichloromethane or acetonitrile. Desired mean particle diameter can be achieved within the range between 200 nm and 10 microm by selecting molecular weights of PEG and dextran, concentration of the co-solution, and PEG/dextran ratio. Increase in molecular weights, concentration or PEG/dextran ratio resulted in increase in particle sizes, and the vice versa. The dextran particles prepared as above showed smooth surface under an electron microscope, a phase transition temperature on thermogram, and sank in carbon tetrachloride (density = 1.592 g/ml), indicating that the particle matrix is dense and glassy. This particulate system and its forming process may have wide applications in formulating variety of pharmaceutical dosage forms and medical devices containing delicate biotech therapeutics.