USE CASES – running
Use Case: Material Science
Target
Development of a mechanistic understanding of the material-process interaction.
Timeline
2017 – 2020
Start
November 2017
Duration
36 months
Main tasks
- Standardisation of existing and derived data & measurement methods
- Review of CM processes and linking of material attributes to process performance for two CM key technologies: feeding and blending
- Elucidate the interaction mechanisms between equipment and material and their effect on process performance
- Raw material, particle and blend performance assessment and property modelling
- Consolidation of CM MS knowledge into a knowledge base
Partner
Use Case: Continuous Coating – Simulation
Target
Simulation of a continuous tablet coating process via CFD-DEM simulation, using the information obtained to scale the process (up or down).
Timeline
2017 – 2020
Start
July 2017
Duration
36 months
Main tasks
- Creation of a model for the GEA ConsiGma™ Pan coater
- Creation of a model including mass and heat transfer
- Understanding of the air flow across the tablet bed as a function of pan geometry (scale issues between the 160 mm and 320 mm pan)
- Understanding of how all air flows in the coater acting together (incoming air, air provided by the air knife and spray pattern air)
- Axial mixing as a function of pan depth
- Optimisation of process parameters for various fill levels, with focus on the 320 mm pan
- Comparison of forces on tablets in the GEA ConsiGma ™ Coater compared to a coater with conventional coating technology
Partner
USE CASES – completed
Use Case: Hot-melt extrusion
- Hot-melt extrusion is inherently continuous
- Solubility enhancement for poorly water soluble compounds with IR tablet as targeted product
Challenges
- Formulation and process development for successful pelletizing
- Formulation for fast dissolution (pellet)
- Formulation and process development for successful tableting (elastic pellet)
- Development of PAT and control strategy
Achievements
- Formulation development for HME material systems with IRrelease profile
- Risk assessment to identify potential CPPs, RTR approaches as well as PAT and control concepts
- Process design of HME line including melt pump, side feeder and granulation system for direct compressible pellets
Partner
Use Case: Wet granulation
- CM equipment available based on wet extrusion granulation (GEA ConsiGma)
- Support migration from batch to continuous processing
- QbD approach to process development
Challenges
- Formulation and process development to mitigate variability in API batches
- Individual unit operation trial and optimization
- Technology/process transfer
- Full line operation support
Achievements
- Extensive material characterization for different API generations and batches
- Elucidation of API raw material property variabilities affecting the processability and consequent formulation optimization
- Management of API generation/batch variability through validated design space
- Confirmation on continuous line and longer runs
Partner
Use Case: Direct compaction
- Simplest process path to CM
- Minimal back-mixing and buffer to damp out disturbance
- Highly dependent on material processability
Challenges
- Interfaces (residues and dead zones)
- Long run process robustness/effects
- In-line PAT method development
Achievements
- Evaluation of the unit operations’ process window by provoking the system with hard-to-process formulations
- Validation of the process stability over longer run time
- Implementation of PAT and development of a control strategy for direct compaction
Partner
Publications
- Martinetz MC, Karttunen A-P, Sacher S, Wahl PR, Korhonen O, Khinast JG:
Modeling of Residence Time Distribution of a Continuous Dry Granulation Tableting Line
– poster presentation @ AICHE 2017, Minneapolis - Martinetz M, Sacher S, Khinast J:
Speed change experiments in a rotary tablet press
– poster presentation @ EuPAT8 2016, Cork - Hörmann T:
Continuous Manufacturing of Immediate-Release Tablets from Hot-Melt Extruded Pellets
– oral presentation @ AiChE, 2015 - Matić J:
Scale-up of HME Process from a Trilobed 16mm to a Bilobed 27mm Extruder; SPH Simulations and 1D Mechanistic Modelling
– oral presentation @ AiChe, 2016 - Rehrl J, Martinetz M, Kruisz J, Sacher S, Horn M, Khinast J:
Model based control concept for a pharmaceutical direct compaction setup
– oral presentation @ IFPAC, 2017, Bethesda - Hörmann TR, Laske S, Koscher G, Khinast JG:
Development of Immediate-Release Tablets Processed via Hot-Melt Extrusion
– oral presentation @ PPS, 2015 - Hörmann TR, Laske S, Koscher G, Khinast JG, Laske S, Koscher G, Khinast JG:
Continuous Manufacturing of Immediate-Release Tablets from Hot-Melt Extruded Pellets
– oral presentation @ AiChE, Annual Meeting, 2015 - Hörmann TR, Wahl P, Gursch J, Laske S, Koscher G, Khinast JG:
Project A3.20a – Use Case HME
– oral presentation @ ECCPM Meeting, 2015 - Rehrl J, Martinetz M, Kruisz J, Sacher S, Horn M, Khinast J:
Model based control concept for a pharmaceutical direct compaction setup
– oral presentation @ IFPAC 2017, Bethesda - Martinetz M, Aigner I, Rehrl J, Scheiblhofer O, Laske S, Khinast J:
Feasibility study for turret speed operating points in a rotary tablet press
– oral presentation @Minisymposium 2016, Graz
Miscellaneous
- Doughty D, Khinast J, Bresciani M, Ketolainen J, De Beer T, Laske S:
CONTINUOUS PROCESSING: The European Consortium on Continuous Pharmaceutical Manufacturing (ECCPM),
European Pharmaceutical Manufacturer, October 2015 (EPM Magazine)