Rapid Determination of Vial Heat Transfer Parameters Using Tunable Diode Laser Absorption Spectroscopy (TDLAS) in Response to Step-Changes in Pressure Set-Point During Freeze-Drying

The purpose of this study was to perform a rapid determination of vial heat transfer parameters, that is, the contact parameter Kcs and the separation distance ℓv, using the sublimation rate profiles measured by tunable diode laser absorption spectroscopy (TDLAS). In this study, each size of vial was filled with pure water followed by a freeze-drying cycle using a LyoStar II dryer (FTS Systems) with step-changes of the chamber pressure set-point at to 25, 50, 100, 200, 300, and 400 mTorr. Kcs was independently determined by nonlinear parameter estimation using the sublimation rates measured at the pressure set-point of 25 mTorr. After obtaining Kcs, the ℓv value for each vial size was determined by nonlinear parameter estimation using the pooled sublimation rate profiles obtained at 25 to 400 mTorr. The vial heat transfer coefficient Kv, as a function of the chamber pressure, was readily calculated, using the obtained Kcs and ℓv values. It is interesting to note the significant difference in Kv of two similar types of 10 mL Schott tubing vials, primary due to the geometry of the vial-bottom, as demonstrated by the images of the contact areas of the vial-bottom.