Sensor for headspace pressure and H2O concentration measurements in closed vials by tunable diode laser absorption spectroscopy

• A tunable diode laser system use for headspace analysis is demonstrated.
• Pressure and H2O concentration are measured simultaneously by differential signals.
• The system is free of inert gas purges and system calibration.
• The accuracy and potential of the system for in-line applications are verified.

The concentration of H2O and the pressure in the headspace of vials are simultaneously measured by a tunable diode laser sensor based on absorption spectroscopy techniques. The 7168.437 cm−1 spectral line of H2O is chosen as the sensing transition for its strong absorption strength and being reasonably far away from its neighboring molecular transitions. In order to prevent interference absorption by ambient water vapor in the room air, a difference between the measured signal and the referenced signal is used to calculate the pressure and H2O concentration in the headspace of vials, eliminating the need for inert gas purges and calibration with known gas. The validation of the sensor is conducted in a static vial, yielding an accuracy of 1.23% for pressure and 3.81% for H2O concentration. The sensitivity of the sensor is estimated to be about 2.5 Torr for pressure and 400 ppm for H2O concentration over a 3 cm absorption path length respectively. Accurate measurements for commercial freeze-dried products demonstrate the in-line applications of the sensor for the pharmaceutical industry.