Sublimation of formaldehyde in freeze-drying

Abstract

Formaldehyde solution, commonly used to inactivate bacterial, rickettsial and viral suspensions during the preparation of vaccines, is known to have a deleterious effect on many antigens during freeze-drying. Sublimation of formaldehyde in shell-frozen and plug-frozen aqueous samples was investigated by measuring the residual formaldehyde periodically during the freeze-drying procedure. It was found that formaldehyde, even while subliming, concentrated on a volume basis. This was more apparent with the plug-frozen than with the shell-frozen material. Moreover, in the preparations taken to dryness, the formaldehyde polymerized to form paraformaldehyde. It was found that the addition of methanol not only prevented polymerization, but also significantly increased the sublimation of formaldehyde without concentration of the latter.