Thermal Effect of Probes Present in a Pharmaceutical Formulation during Freeze-Drying Measured by Contact-Free Infrared Thermography

Abstract

A high-resolution infrared (IR) camera was used for temperature measurements in a pharmaceutical formulation (mannitol/sucrose solution, 4:1%, m/m) during a freeze-drying process. The temperature was measured simultaneously at the surface as well as vertically (e.g., in-depth) along the side of custom-made cuvettes equipped with a germanium (Ge) window. Direct imaging during 45 h from −40 °C to 40 °C took place every 60 s on the surface and on the side with 0.28 × 0.28 mm per IR-pixel providing 2700 thermograms. The spatial resolution per cuvette was approximately 4225 pixels for the surface view (without a probe) and 6825 IR-pixels for the side view. Temperature effects and gradients due to the presence of a Pt100 and a LyoRx-probe in the pharmaceutical formulation were clearly visible and were quantified during the freezing step as well as the primary and secondary drying stages. The temperature was about 3.5 K higher during primary drying as compared to the temperature measured in the same material in adjacent cuvettes without probes. During secondary drying, evaporative cooling of upper layers was clearly visible.