Optimizing Medical Freeze Drying | Lyophilization < 2 Torr
Scientific Vacuum Measurement & Control Equipment are used in Medical Freeze Drying Applications to Help:
- Create bulk and active ingredients (API) for drug products
- Mainly used to improve the stability and storage of easily altered drugs and to protect high value products from oxidation or damage during processing
- Commonly applied to the production of injectable dosage forms of drugs, pharmaceutical freeze–drying is also used to produce diagnostics
- Freeze drying is also used in botanical processing to preserve the integrity and beneficial chemical properties of the flower
Lyophilization, also known as freeze drying, is a process used for preserving biological material by removing the water from the sample, which involves first freezing the sample and then drying it, under a vacuum, at very low temperatures.
The low pressure environment helps minimize oxidation during drying. The vacuum pressure typically used in freeze drying applications is less than 2 Torr down to around .05 Torr.
Quick Conversion Chart 2 Torr down to .001 Torr
| 2 Torr | .05 Torr | |
| Microns | 2000 Microns | 50 microns |
| mbar | 2.67 mbar | .067 mbar |
| kpa | .27 kpa | .007 kpa |
| Pa | 267 Pa | 6.67 Pa |
| PSI-A | .039 PSI-A | .001 PSI-A |
Lyophilized samples may be stored much longer than untreated samples. The resulting precipitate is a shelf-stable powder. This powdered drug is later reconstituted at point of care for patient use.
Importance of Optimizing Your Freeze Drying Control
Formulations undergoing freeze‐drying can be sensitive to deviations in temperature and chamber vacuum pressure, which may be exacerbated in a freeze dryer with non-optimal temperature and chamber pressure control, leading to losses in process efficiency and stresses that can affect the quality of the drug product .
Freeze drying has several steps:
- Preparation and pretreatment
- Pre freezing for solidifying water
- Primary Drying
- Secondary Drying
Primary drying is the step that can take the longest and is where optimization is a key to success.
Freeze drying works by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate resulting in a dry, structurally intact product.
Sublimation means going from its solid (frozen) state to its gaseous state without ever passing through its liquid phase.
The sublimation rate of a frozen product depends on the difference in vapor pressure of the product compared to the vapor pressure of the freeze drying condenser. The molecules migrate from the area of high-pressure to the lower pressure area. This balancing act is the key to optimum drying.
One area of optimizing the efficiency of the drying process is to monitor the primary drying phase and know when you have decreased the moisture content enough to end this process step.
Optimize your process by knowing when the primary drying phase is complete. The freeze drying process isn’t complete when primary drying is done, but this is the longest step in the drying process so optimizing this step can save you a lot of time. The primary drying step can take up to double the time of the secondary drying phase.
The secondary drying process helps you remove bound or residual moisture content that could still be as high as 7-8%. Continued drying is necessary at a warmer temperature to reduce the residual moisture content to ideal values.
Optimizing Primary Drying
FYRA for End of Primary Drying Detection
Will help you detect when most of the water or residual solvent from a product has been removed or the end of primary drying has been reached in a vacuum drying application.
Background on How this FYRA End of Primary Drying package works:
When a freeze dryer is equipped with both a thermal and direct measurement, these sensors can be utilized to indicate the end of primary drying by indicating a converging pressure delta between the 2 sensors (Source).
Vacuum Measurement for Freeze Dryers
DigiVac has been designing and manufacturing controllers (ODM/OEM) for freeze dryers for over 30 years. The core product for freeze drying vacuum measurement used widely is the Model 22W, which is available with and without a display.
Ultra Compact thermocouple vacuum transmitter. Active gauge and vacuum transmitter with display (also available without display) that measures from .001 to 760 Torr. Best accuracy from .001 Torr to 5 Torr.
Active gauge can easily be popped off included 531 sensor and switched out/no tools required
- Includes RS232 and 5 Volt Analog output
- Bright LCD display for local reading of vacuum pressure
- Applications: freeze dryers, refrigeration systems, assembly lines, vacuum ovens, laboratory
Range: 0.001 – 760 Torr
0 to 0.009 Torr +/-0.002 Torr
0.010 – 2.00 Torr +/-15% of reading
2.00 Torr to 5 Torr +/- 1 Torr
5 – 760 Torr – Continuous and monotonic
As you can see from these accuracy specifications, the choice of thermocouple vacuum sensing technology has excellent accuracy for the freeze drying application range of vacuum and is a very economical choice.
For OEM operations, this is an active gauge that is available without an enclosure (electronics and sensor only) to function as a PLC transmitter within a freeze dryer. For more information on how this linearized analog output works click here.
Increase Molecular Flow to Speed Drying Process with the StrataVac Bleed Vacuum Controller or the FYRA Bleed Vacuum Controller
The StrataVac bleed vacuum controller or the FYRA Bleed Vacuum Controller (UL, CSA) helps increase molecular flow and throughput.
- Ideal for controlling vacuum level in freeze dryers
- Rich remote command line interface for integration with PLCs (Link for is FYRA commands)
- Bleed in inert gasses like air, nitrogen, or argon to increase molecular flow and speed drying process by helping to sweep out trapped moisture in the vacuum chamber
- Accuracy Range: .001 Torr to 6 Torr
- Control Range: 1 Micron to 6000 Microns (.001 Torr to 6 Torr)
- When ordered with a NIST traceable certification can be used as a cGMP reference
Have An Older Freeze Dryer That The Vacuum Gauge Has Gone Bad?
Our Model 215V is an excellent replacement for an older freeze dryer with a failed onboard vacuum gauge. The Model 215V is a vacuum process controller with RS232 and 2 set-points.
This controller has leads that are long enough to install inside the freeze dryer for simple vacuum set-point process control.
Need To Troubleshoot Your Freeze Dryer To Confirm If Your Onboard Vacuum Gauge Is Functioning?
Choose the Bullseye Precision Gauge with 536 KF25 Sensor
Portable Vacuum Gauge with rugged sensor
- More accurate than most OEM vacuum gauges that are integrated in the freeze-dryer, and when ordered with a NIST certification can be used as a cGMP reference
- Patented vacuum gauge includes an Agilent 536 sensor that has an integrated baffle that provides protection and helps reduce sensor failure.
- Has 12 measurement units for implementation in almost any vacuum application (Torr, mbar, bar, kPa, inches of Hg, mm Hg, millitorr, microns, inches of water, PSI, Pa)
- Measurement range: .001 Torr to 760 Torr
- Range with Accuracy: .001 Torr to 6 Torr
Why partner with DigiVac?
DigiVac has been designing and manufacturing scientific measurement, control instruments and freeze dryer controllers since 1983. We can also work with you on custom solutions with our team of software and hardware engineers. Our customers appreciate our attention to detail, predictable lead times and the ability to respond quickly to customer urgency.
