Finding the End of the Granulation Process

Aug 16, 2011
By PharmTech Editors
Untitled Document

Q: Our facility manufactures several products, and, from time to time, we must process ingredients that we haven’t encountered before through wet granulation. We try to use previous experience to develop the optimal granulation process for each new ingredient, but we sometimes get it wrong. Many times, we’ve taken materials from the granulator only to find that they exhibit poor flow and insufficient density. How can we easily determine the end point of a given granulation process?

A: One solution is to track wet granulation using a powder rheometer. Powder rheometers characterize samples by measuring them in motion. Basic flow energy (BFE), a dynamic powder parameter, can be a sensitive marker of the transition point from wet mass to granules and a precise tool for detecting when granules have attained their optimal properties.

BFE is the energy required to induce a specific flow pattern in a conditioned powder bed. One can measure BFE with a powder rheometer easily using wet samples taken directly from the granulator. Pause the granulation, extract a representative sample for measurement directly into the flow vessel of the powder rheometer, and continue processing if necessary.

To ensure a homogenous, representative sample, avoid the areas around the spray nozzle and walls, where material tends to be less uniform. Use large sample sizes for large granulates to ensure representative sampling of the batch. Automated measurement protocols can make the measurement fast and highly reproducible. The axial and rotational forces acting on a helical blade as it rotates through the sample are precisely measured to quantify the resistance of the bed (through BFE), which is governed by the properties of the wet granulate.

As water content increases, BFE climbs slowly, and it rises sharply at concentrations coincident with the end point. Physical examination of the samples suggests that this sharp rise corresponds with the transition from wet mass to granules.

Because BFE is independent of scale, it is of great value when switching from laboratory to pilot to commercial scale. Processing to an endpoint defined in this way gives the operator scope to vary conditions in response to changing feed, scale, or equipment. The approach also is consistent with quality by design.

—Tim Freeman, director of operations for Freeman Technology

 

If you have a problem with your equipment or process, an industry expert may have the solution. Please send your question to Erik Greb, editor of Equipment and Processing Report, and we may be able to provide an answer in a future issue. All questions will remain anonymous.