Morphology of protein particles produced by spray freezing of concentrated solutions

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 65; no. 2; pp. 149 - 162
• Main Authors: Engstrom, Josh D., Simpson, Dale T., Lai, Edwina S., Williams, Robert O., Johnston, Keith P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-02-2007; Elsevier Science
• Subjects: Algorithms; Biological and medical sciences; Freezing; General pharmacology; Humidity; Leidenfrost effect; Liquid cryogen; Medical sciences; Microscopy, Electron, Scanning; Muramidase - chemistry; Nitrogen; Particle Size; Pentanes; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders; Proteins - chemistry; Solutions; Spray freeze-drying (SFD); Spray freezing into liquid (SFL); Trehalose; Viscosity; Spray freezing into liquid (SFL); Liquid cryogen; Spray freeze-drying (SFD); Leidenfrost effect; Particle; Freeze drying; Pharmaceutical technology; Morphology; Spray drying; Freezing; Protein; Solution
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2006.08.005

The mechanisms for the formation of high surface area lysozyme particles in spray freezing processes are described as a function of spray geometry and atomization, solute concentration and the calculated cooling rate. In the spray freeze-drying (SFD) process, droplets are atomized into a gas and then freeze upon contact with a liquid cryogen. In the spray freezing into liquid (SFL) process, a solution is sprayed directly into the liquid cryogen below the gas–liquid meniscus. A wide range of feed concentrations is examined for two cryogens, liquid nitrogen (LN2) and isopentane (
i-C5). The particle morphologies are characterized by SEM micrographs and BET measurements of specific surface area. As a result of boiling of the cryogen (Leidenfrost effect), the cooling rate for SFL into LN2 is several orders of magnitude slower than for SFL into
i-C5 and for SFD in the case of either LN2 or
i-C5. For 50
mg/mL concentrated feed solutions, the slower cooling of SFL into LN2 leads to a surface area of 34
m
2/g. For the other three cases with more rapid cooling rates, surface areas were greater than 100
m
2/g. The ability to adjust the cooling rate to vary the final particle surface area is beneficial for designing particles for controlled release applications.