Atmospheric Spray Freeze-Drying on Common Biologics and Excipients as a Comparison to Lyophilization

• Author / Creator

  Ly, Alvin

• Atmospheric spray freeze-drying (ASFD) is an alternative freeze-drying process to conventional vacuum freeze-drying. ASFD involves spray-freezing biologics of interest in a feedstock into a cold freezing chamber. Cold drying gas passes through the chamber at a high flow rate to sublime the water and ice in the powder with convective forces. ASFD is a seven-hour drying process compared to conventional freeze-drying which is in the order of days. Ertapenem, a regularly used antibiotic, and trehalose, a biologic stabilizer in freeze-drying, were freeze-dried at varying feedstock concentrations. Ertapenem was freeze-dried at 50, 100, 150, and 200 mg/mL; higher concentrations had pale yellow discoloration in both liquid and dried powder. Although ASFD ertapenem was porous compared to the lyophilized counterpart, higher feedstock concentrations yielded larger particles with lower porosity. Trehalose was freeze-dried at 100, 200, and 300 mg/mL. ASFD trehalose at lower concentration existed as a free-flowing powder whereas higher feedstock concentration yielded a thin brittle cake. Both trehalose and ertapenem powders at lower feedstock concentrations made powders with large pores and high void fraction, which have excellent wetting and aerodynamic properties. Bacteriophage D29 in solutions with varying concentration of mannitol and trehalose, were freeze-dried using ASFD. A solution of trehalose and mannitol at a mass ratio of 7:3 and a total feedstock concentration of 100 mg/mL had the lowest titer reduction of ~0.6 logs with a powder moisture content of 4.9±0.1 %. In comparison, pure trehalose and 1:1 ratio of trehalose and mannitol both had titer reductions larger than 1.5 logs. Raman spectroscopy of the powders showed that trehalose in the powder remained amorphous while mannitol completely crystallized, which are desirable for preserving phages in a dry solid form. The short drying process, improved wetting properties, and the ability to preserve bacteriophages makes ASFD an attractive alternative to conventional freeze-drying.

• Subjects / Keywords

  • Freeze-Drying
  • Powder Formation

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-dnac-ya43

• License

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