Research

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

  1. 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
  2. Martinetz M,  Sacher S,  Khinast J:
    Speed change experiments in a rotary tablet press
    – poster presentation @ EuPAT8 2016, Cork
  3. Hörmann T:
    Continuous Manufacturing of Immediate-Release Tablets from Hot-Melt Extruded Pellets
    – oral presentation @ AiChE, 2015
  4. 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
  5. 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
  6. Hörmann TR,  Laske S, Koscher G, Khinast JG:
    Development of Immediate-Release Tablets Processed via Hot-Melt Extrusion
    – oral presentation @ PPS, 2015
  7. 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
  8. Hörmann TR, Wahl P, Gursch J, Laske S, Koscher G, Khinast JG:
    Project A3.20a – Use Case HME
    – oral presentation @ ECCPM Meeting, 2015
  9. 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
  10. 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

  1. 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)