Dr Michael Braun, Boehringer Ingelheim Pharma
Dr Jean-Denis Mallet, Former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS
Dr Harald Stahl, GEA
Prof Dr Karl G. Wagner, University of Bonn
A thorough root cause analysis often reveals that compression issues such as capping, sticking and weight variations are 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 tabletting 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.
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Fundamentals of granulation – what is a good granulate?
- 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
Fundamentals 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
Scale-Up of Fluidbed Granulation
- Fundamentals of Fluidbed Granulation (process & technology)
- Which process parameter influences which product quality attribute
- How to scale-up?
- Consequences for the quality critical attributes
High Shear Granulation: Fundamentals
- Plant-geometry and -design
- Process parameters (degree of filling, impeller speed, liquid saturation, process time)
- Methods of drying
- Special Case: Single-Pot-Granulation
High Shear Granulation: Scale-Up
- Influence of impeller speed, liquid addition rate and wet massing time
- Review of end point detection methods
- Scale up trouble shooting
Fundamentals of Roller Compaction / Dry Granulation
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
- 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
Wrap-Up: Overview and comparison of the different granulation techniques - An Outlook
- 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
- Continuous Manufacturing
- Factors for a 6-sigma granulation process
- Which optimisation is possible by using continuous Granulation
- Control of continuous processes
Tableting: Process, Equipment and Formulation
- 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
- Comparison of the different control philosophies
- Measurement of the deformation behaviour by compression analysers
- Overview and characterisation of the most important excipients used for compression
Scale-Up of tableting processes
- 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
Global requirements for OSD operations
- 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
- How much containment is really needed
- Identification of critical operations (with regards to exposition)
- Comparison of different containment concepts
- Examples of existing equipment
Validation of a tableting process
- Main Pharmacopoeial descriptions for tablets
- What are the main validation requirements
- Tablets Quality Attributes and Tableting 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
Trouble shooting in tableting processes: Sticking, Capping & Lamination
- 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