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.

Keywords

• freeze-drying
• lyophilisation
• infrared thermography
• high resolution
• pharmaceutical formulation
• depth profile