Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Abstract

Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2–4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.

Complexing Protein-Free Botulinum Neurotoxin A Formulations: Implications of Excipients for Immunogenicity

“…The addition of ionic salts, such as NaCl, is considered critical in a lyophilization process [122] because it may also negatively affect the freeze-drying process. In some cases, however, the addition of NaCl improves the appearance of the cake of the freeze-dried materials without affecting its bioactivity [123]. For BoNT/A, it was reported that the presence of NaCl during the freeze-drying process results in a loss of bioactivity [124].…”