Dr Michael Braun, Boehringer Ingelheim, Pharma, Director Late Stage Drug Product Development
Dr Jean-Denis Mallet, former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS
Dr Harald Stahl, GEA, Group Director Application & Strategy Management
Prof Dr Karl G. Wagner, University of Bonn, Professor for Pharmaceutical Technology at the University of Bonn
A thorough root cause analysis often reveals that compression issues such as capping, sticking and weight variations are often related to the upstream granulating process. The objective of this intensive training is therefore to provide a deeper insight into functional relationships between granulation and tableting in order to avoid such problems from the very beginning.
The training also conveys a deeper understanding for tableting and granulating processes, including Scale-Up, which helps in avoiding problems or solving them in practice. This also complies with the GMP principle of understanding and controlling the critical parameters of manufacturing processes. An introduction to the different GMP requirements for manufacturing solid dosage forms worldwide is therefore also subject of this course.
Granulation and tableting are considered the most commonly used manufacturing processes in the pharmaceutical industry. Of course, a direct compression process is most preferred; in practice, however, an upstream granulation is usually required to obtain a favourable particle size distribution, flowability and compactibility. Different requirements for granulates call for different procedures or technologies. Nowadays, fluid bed, high-shear or dry granulation are the most commonly used processes. An important part of this course is therefore to introduce the different granulation methods, their basic principles and Scale-Up approaches. A deeper insight into process parameters and their influence on product properties is also part of the programme.
The holistic approach to granulation and tableting therefore aims at avoiding issues from the very beginning and to overcome problems at an industrial scale through in-depth process insights. A separate block of this seminar is dedicated to the issue of Trouble Shooting. Please bring your questions concerning manufacturing problems with you or send them in beforehand.
These challenges are met by new excipients, new control algorithms for tablet presses, laminations as well as special punches and dies. Having the presses run slower should be a last resort after all other options have failed.
Further topics of this training are the tableting of highly active materials, the implementation of recent validation requirements based on the example of tablet manufacturing as well as continuous manufacturing.
This intensive course is designated for all professionals from Pharmaceutical Development, Production and QA/Regulatory Affairs, who are responsible for the development, the routine production or the Scale-Up and transfer of tableting processes.
Fundamentals of granulation – what is a good granulate?
Fundamentals of Roller Compaction / Dry Granulation
- Reasons for granulation
- Overview of the different granulation processes
- Impact of the single processes on the granulate properties
- Understanding the mechanisms of agglomeration
- Characterisation of granulates
- Excipients for granulation and their impact on product properties
Dry granulation is gaining more and popularity in the pharmaceutical industry as it may offer advantages like fast development and Scale-Up, usability in continuous manufacturing operations and improved process control
Fundamentals of Fluidbed-Granulation
- Design aspects of a modern roller compactor
- Impact of process parameters like compaction force, gap, roll speed, roll surface, roll width and side seal system on ribbon properties
- Principles of densification: solid fraction as critical material attribute
Scale-Up of Fluidbed Granulation
- Design aspects and working principle of a modern fluidbed dryer
- Basic principle and advantages of fluidbed granulation
- Impact of process parameters on product properties
- Process insights: how to run, control and design the process
High Shear Granulation: Fundamentals and Scale-Up
- Fundamentals of Fluidbed Granulation (process & technology)
- Which process parameter influences which product quality attribute
- How to scale-up?
- Consequences for the quality critical attributes
Wrap-Up: Overview and comparison of the different granulation techniques
- Plant geometry and design
- Process parameters (degree of filling, torque-speed, humidity, time)
- Methods of drying
- Special Case: Single-Pot-Granulation
- Scale-Up: influence of impeller speed, dosing speed
Fundamentals of tableting/compression and tablet-presses
- How to choose the right one?
- Which technique for which kind of product: viewpoint of development
- Which technique for which product portfolio: viewpoint of production
- Comparison of direct and indirect cost: viewpoint of management
Excipients for tableting: their selection corresponding to their mechanical compatibility
- Physical fundamental of powder adhesion
- Compressibility and compactibility of different materials
- How to quantify these properties?
- How to handle materials with unfavourable compression properties?
- Parts of tablet presses: their function and their impact on product properties
- Special cases: effervescent tablets
- Comparison of the different control philosophies
Scale-Up of tableting processes
- Fundamentals of deformation and cohesion of tablets
- Measurement of the deformation behaviour by compression analysers
- Overview and characterisation of the most important excipients used for compression
- Practical task: selection of appropriate API and excipient combinations
- Case Studies
Global requirements for OSD operations
- Compression issues during Scale-Up and Transfer Quality by Design helps to overcome Scale-Up issues
- Scale-Up and optimisation of compression processes
- Constant dwell time as Scale-Up approach: theory and practice
- Case studies
Validation of a tabletting process
- OSD Quality Attributes: from homogeneity to dissolution
- Pharmacopoeias and OSD : main monographs
- Requirements from the main guides: US, EU/PICS & WHO
- Requirements from special chapters: US, UK and France
Handling of highly potent materials – containment for tableting processes
- Main Pharmacopoeial descriptions for tablets
- What are the main validation requirements
- Tablets Quality Attributes and Tabletting Critical Parameters
- Establishing a protocol not forgetting intermediate steps
- Running the process not neglecting secondary operations
- Writing a clear and trustful report
- Following tablets stability issues
- How much containment is really needed
- Identification of critical operations (with regards to exposition)
- Comparison of different containment concepts
- Examples of existing equipment
Trouble shooting in tableting processes: Sticking, Capping & Lamination
- Factors for a 6-sigma granulation process
- Which optimisation is possible by using continuous granulation
- Control of continuous processes
- The Consigma Systems as one example for continuous manufacturing equipment
- Reasons for tableting problems
- Possible changes in upstream processes
- How to improve compression properties
- Tips and tricks for production: possible changes within the existing equipment and registration environment
Final part of the course is an open discussion where
you will find help for your special cases. Bring your questions/problems/troubles with you to the course or send them beforehand so that the speakers can prepare themselves for finding answers. Send your cases to firstname.lastname@example.org, subject: “Trouble-Shooting Tableting”