A standard method for checking the vacuum in sealed vials containing freeze-dried (lyophilised) product has been the spark test. In this method the vials are exposed to a high voltage. A resulting glow discharge in the headspace of the vial indicates the presence of some level of vacuum. Drawbacks to this method include a limited measuring range (0 - 250 mbar) and the possibility that protein-based biological product can be damaged by the high voltage. A revolutionary method has now been developed to quantitatively measure the headspace pressure inside a vial using laser absorption spectroscopy.
Light from a near-infrared semiconductor laser is tuned to match the internal vibrational frequency of a target molecule. The light is passed through the headspace region of a sealed container and some of the laser energy is absorbed by the target molecules. The laser is scanned in frequency and a photodetector records an absorption profile. The laser absorption signal contains information about the headspace gas concentration and the total headspace pressure. The measurement method also incorporates a high sensitivity detection technique known as frequency modulation spectroscopy (FMS). This results in a measurement sensitivity that is 104 greater than traditional direct absorption spectroscopy.
Developed by Lighthouse Instruments LLC, this laser absorption technique solves the drawbacks of the spark test method. Headspace pressure measurements can be made over the full range (0 - 1 atm). Since the laser light simply passes through the headspace of the vial, there is no affect on the product. Bonfiglioli Pharma Machinery has incorpo-rated the Lighthouse Instruments optical platform to launch a new rapid and non-destructive vacuum tester.
Absolute pressure or vacuum level in a pharmaceutical container can be determined by measuring the pressure broadening of a water vapor (moisture) absorption line. Light from a tunable semi-conductor laser is directed through the headspace region of a container. The laser light is tuned in frequency to match the internal absorption frequency of moisture molecules at 1382 nm. The width of the resulting moisture absorption signal is directly proportional to total head-space pressure. This means that a direct quantitative measurement of the vacuum level in the container can be made using this method. Note that moisture is always present in the headspace due to water molecules in the cake that evaporate and remain in equilibrium in the headspace as residual water vapor.
To measure oxygen concentrations the laser light is tuned in frequency to match the internal absorption frequency of oxygen molecules at 760 nm. The vacuum level in the container can be inferred from the measured headspace oxygen levels. The absorption signal is proportional to oxygen concentration (noted to the right of each scan). The compact LVA machine as seen in the photo is fully computerised utilising a SCADA platform. Both Moisture or Oxygen Absorption is available for vacuum testing. The software is easy to operate and includes utilities such as a products database, Statistical reports etc. A printer is also installed for printing test results and parameters. The output may easily reach 400cpm. Vials may range up to 150ml and may be both amber or transparent. Laboratory semi-automatic models are also available.
- Bonfiglioli Pharma Machinery