<b>Pirani Gauge: Function, Calibration, and Use in Pharmaceutical Freeze-Drying</b>

<p dir="ltr">A <b>Pirani gauge</b> measures pressure based on <b>thermal conductivity</b>. It contains a heated filament whose temperature (and thus electrical resistance) changes as gas molecules collide with it. The <b>rate of heat loss depends on both pressure and the type of gas</b>, allowing the device to convert filament resistance into an electrical signal proportional to pressure, typically in the range of 10⁻³ to 1000 mbar.</p><p dir="ltr"><b>Gas Sensitivity:</b><br>Pirani gauges are <b>more sensitive to water vapor</b> than inert gases like nitrogen. During freeze-drying, this results in <b>higher readings while ice is sublimating</b>, and the signal decreases as sublimation slows. Importantly, the <b>end of ice sublimation can occur during (but often around the midpoint) of the step-down in the Pirani signal</b>, meaning the gauge alone cannot precisely identify the sublimation endpoint. Other conventional sensors, such as thermocouples, <b>cannot resolve the endpoint either</b>, because they are also influenced by water desorbing from the product solids, whereas the capacitance manometer only serves as the base line against which the final Pirani gauge reading may be judged. </p><p dir="ltr"><b>Use in Freeze-Drying:</b><br>For accurate determination of the primary drying endpoint, <b>Through-Vial Impedance Spectroscopy (TVIS)</b> can be used, as its signal is not affected by water desorption from solids. Once TVIS identifies an approximate endpoint on the Pirani signal, <b>a cycle can be run to ramp (slowly) to secondary drying</b> to validate the prediction and optimize the hold time.</p><p dir="ltr"><b>Calibration:</b><br>Calibration is performed against <b>reference pressures with the same gas composition</b>, ensuring reliable readings during freeze-drying. Corrections may be required if the chamber gas composition changes.</p>