Granulation - Process, Scale-Up, Trouble Shooting

Programme

Fundamentals - what is a good granulate
Even there is a recent trend to use often dry methods
in the production of solid dosage forms granulation remains for 2 reasons to be one of the most important unit operations. First it allows the use of simpler and cheaper excipients which is of paramount importance if large volume products have to be produced and second granulation can massively improve the compression behaviour of materials.

• Overview of granulation methods
• Theory of granulation
• Benefits and limitations

Fundamentals – high shear granulation
High shear granulation is a popular granulation method. It is a robust granulation technique capable of handling most APIs, to produce granules of intermediate densities, between roller compacted and fluid bed processed granules. Operationally, control of the shear energy input for granulation is by changing the impeller speed. Design of the impeller and feed load have their effects on the granulation process. Thus, together with the impeller speed, the method and rate of liquid addition are also important critical process attributes to control the granulation process.

Fundamentals – fluid bed granulation
Fluid beds were first adopted by the pharmaceutical industry for drying granules after wet massing. Later, fluid bed granulation was introduced, to produce free flowing, spherical and porous granules direct from powders. The fluid bed granulator depends entirely on the fluidising air to lift and dry particles. The liquid addition rate and method of delivery system are important control determinants of the granulation rate. Various innovative changes have improved the fluid granulation processors. A discussion of the fluid bed technique and innovations to the fluid bed granulation processor will be provided.

Dry Granulation / Roller Compaction
Dry granulation is a common unit operation in solid dose manufacture. Small footprint, fast process development and scale-up, together with the option for continuous manufacturing are compelling arguments why roller compaction has become even more important for pharmaceutical industry nowadays.
Enhanced product and process understanding, following a Quality by Design approach, is key for a successful technology transfer to operations and smooth implementation in routine manufacture.

The session will cover following topics:
I

• ntroduction and basic principles of roller compaction
• Scale-up and process monitoring
• Case studies

Even high shear granulation processes are already in use for many decades still scale up is often done by trial and error. In this session more scientific approaches are introduced.

• Theory of high shear granulation
• Identification and scale up of CPPs
• The role of the end point- review of available technologies
• The importance of suitable equipment and instrumentation

Scale-up fluid bed granulation
By their nature fluid bed processes can be much easier described by scientific models than high shear processes. However often these possibilities of science based scale up approaches have been ignored.

• Theory of fluid bed processes
• Identification and scale up of CPPs
• The importance of suitable equipment and instrumentation

Scale Up of wet granulation processes: Practical aspects
Wet granulation processes, like fluid-bed and high shear granulation, have been widely applied for decades in pharmaceutical industry. Although multiple scale-up models and approaches are described in literature, mechanistic process understanding is still not yet mature. This session will focus on translation and relevance of different scale-up models into practice.

• High shear and fluid-bed granulation: theoretical scale-up considerations
• Case study: Scale-up of a high shear process
• Case Study: Scale-up of a fluid-bed process

New Trends in Granulation: PAT, continuous manufacturing, etc.
Continuous processing is widely used in other industries such as food or chemicals. Over recent years also the pharmaceutical industry showed an increasing interest as well as authorities pushing for a wider use.

• Why go continuous?
• Examples of installations
• Regulatory situation
• Control strategy

Trouble-Shooting Workshop
In this interactive session, all the key elements of the preceding lectures are brought together. A systematic approach is presented and discussed with regards to the extent, trouble shooting measures have to be escalated: what can be done on the operator level, what can be done on the supervisor level, what must be done by development.