Freeze Dryer Characterization using Water Sublimation Tests and Applications for Lyocycle Scale-Up

Freeze Dryer Characterization using Water Sublimation Tests and Applications for Lyocycle Scale-Up


Description:
Purpose: To compare lab, pilot, and production-scale freeze dryers using water sublimation tests. Sublimation tests will be used to (i) identify shelf to shelf variation and map the lyophilizer with respect to sublimation rate (ii) evaluate the maximum sublimation rate attainable without overloading the freeze dryer (iii) calculate the vial heat transfer coefficient for various locations in the freeze dryer.
Methods: Using Water for Injection (WFI), the sublimation rate, determined gravimetrically, was evaluated for lab, pilot, and production-scale freeze dryers. Steady-state heat and mass transfer relationships relevant to freeze drying were used to calculate the heat transfer coefficients and overloading conditions for each freeze dryer evaluated. The heat transfer coefficient was used to model primary drying using Passage Freeze Drying software.
Results: The sublimation tests in trays demonstrated that failure of the freeze dryer (e.g. loss of pressure control) might occur if the sublimation rate exceeds the thermal load capacity. The sublimation tests also demonstrated that the sublimation rate in vials increased towards the rear of the freeze drying chamber (closest to the pipe separating chamber and condenser) and typically the lowest sublimation rates were observed on the middle shelf, indication of the “coldest zone” of the lyophilizer. The heat transfer coefficient for various locations on a shelf is also dependent on the scale of the freeze dryer. For example the heat transfer coefficient for center vials in a pilot-scale freeze dryer was approximately half of the heat transfer coefficient calculated for center vials in a lab-scale freeze dryer. The PassageÒ Freeze Drying software predicted relative drying times that were consistent with experimental data for sublimation endpoint for various size lyophilizers.
Conclusion: Data acquired from water sublimation tests can be used to ensure the freeze dryer can sustain a thermal load for specified lyocycle conditions. Sublimation test data is also used to determine hot/cold zones in the lyophilizer that should be identified as areas interest for post-lyophilization testing such as water content and reconstitution time. Sublimation test data can be also be used to compare equivalence of various capacity dryers and the Passage Freeze Drying software can be used to predict the endpoint of ice sublimation which is extremely valuable for lyocycle scale-up.

CFD Consulting

CFD Consulting - Flow Modeling Software - Discrete Element Modeling - CFD Flow Software: "Technalysis' CAE & CFD Consulting and SoftwareSince 1985, Technalysis has been providing advanced CAE technology involving fluids, materials and manufacturing processes within wide range of industrial applications with its Technalysis® Consulting and Passage® Software.
Technalysis specializes solving complex fluid flow and heat transfer problems using computational fluid dynamics and other advance CAE solutions.
Technalysis' CAE - CFD flow modeling capabilities can fully support or complement and enhance clients engineering capabilities in product design and manufacturing.

Water Pump Design Software - Technalysis' CAE Engineering - CFD Software

Water Pump Design Software - Technalysis' CAE Engineering - CFD Software: "Technalysis' CAE Expertise in Water Pump and Other Fluid Flowing Equipment DesignPASSAGEÒ software is a proven predictor of flow performance in pumps and other fluid moving equipment. The method used for water pump design focuses on analyzing the impeller and impeller housing and matching their combined performance. The results from flow models are evaluated to determine the impact of pump geometry on performance, flow capacity, and cavitation.
The flow characteristics of the housing are evaluated by analyzing velocity and pressure distribution inside the housing and the flow behavior around the tongue area (cut off). The major design parameters studied include pressure gain of the housing, areas where losses are occurring, the effectiveness of the tongue design, circulation inside the housing, and flow distribution at the housing exit. The combined performance of the impeller and the housing are matched to optimize the performance of both components.
Technalysis furnishes design services to meet the objectives of your next pump requirement by:
· Evaluating current water pump performance
· Establishing impeller and housing changes for performance improvement:

1. increased water pump capacity
2. improved water pump efficiency
3. and elimination of cavitation"

Freeze Drying Process – Simulation of Pharmaceutical, Chemical and Food Freeze Drying Processes

Freeze Drying Process – Simulation of Pharmaceutical, Chemical and Food Freeze Drying Processes: "Freeze Drying Process - PASSAGEâ/Freeze Drying SoftwarePassage®/FreezeDrying is a computer program designed for the simulation of freeze drying processes in vials and pans.
Passage®/FreezeDrying provides modeling of containers with axisymmetric boundary conditions with both primary and secondary drying simulation capabilities. The software also handles containers with asymmetric boundary conditions, as in the case of vials placed in corners or near the walls of freeze-drying ovens.
The user-friendly, interactive preprocessor accepts externally generated meshes and support automatic entry of material properties, process conditions, and display of geometry.
Passage®/FreezeDrying also has user-friendly, interactive post-processing modules which display the computed temperature, vapor concentration, water pressure, and glass transition distributions in the form of contour plots and x-y graphs. Animation of sublimation front movements can also be obtained easily.
Some objectives of using CAE is to identify freeze drying process conditions to:
Maximize drying rate and increase production
Prevent chemical & structural degradation
Provide uniform drying throughout the material
Predict drying time for primary and secondary stages to desired levels of water concentration

Some results of the analysis:
Time for primary and secondary drying of products
Location for isolated islands of ice in pan drying
Concentration contours
Absorbed water concentration
Interface position in time
Sublimation frontal movement
Temperature contours and history
Water pressure contours

FreezeDrying brochure "

Mold Flow Software & Design - Compression - Injection Molding

Mold Flow Software & Design - Compression - Injection Molding: "PASSAGE®/COMPRESSION is a finite element program for the mold filling simulation of complex three-dimensional, thin-walled parts.
Flow models include: Barone-Caulk hydrodynamic friction and generalized Newtonian fluid to simulate the non-isothermal filling of SMC, BMC, and glass; fiber orientation for SMC and curing kinetics for thermosets.
A high-pressure in-mold coating simulation option is also available.
A user-friendly preprocessor allows mesh generation and capability to accept externally generated
meshes with interactive entry of process conditions and numerical control parameters.
Results are viewed with an interactive post-processor that features dynamic rotation and zooming animation of results, and viewing options for color contour and vector plots."