Experimental and Modeling Study During Freeze Drying of Aqueous tert-Butanol–Based Formulations in Vials

Abstract

In this study, using COMSOL Multiphysics software, we set up a two-dimensional model for the sublimation step a frozen aqueous organic cosolvent tert-butyl alcohol (TBA) formulation without a dissolved active principal ingredient contained in 4-mL glass vials. This model, based on the hypothesis of a sublimation process mainly governed by the conductive heat transfer between the shelf and the sublimation front, allowed precise prediction of the sublimation kinetics and the sublimation front movement for different operating conditions. Next, this modeling was validated by many experimental runs under operating conditions corresponding to very low total gas pressures (5 to 50 Pa) and low shelf temperatures (0 to −20°C) generally encountered during industrial freeze drying of thermosensible pharmaceuticals (vaccines, diagnostic proteins, serums, etc.).

Keywords:

• Freeze drying
• Modeling
• Pharmaceuticals
• Sublimation
• tert-Butyl alcohol

Notes

^a Sublimation T_shelf = 0°C and P_c = 6 Pa (4-mL glass vial).

^a 4-mL glass vial.

^a 4-mL glass vial.