At the 2009 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles, Gerald Burke presented a case study on how Patheon Pharmaceuticals improved roller compaction processes. Specifically, the case study focused on the influence of roller compactor settings on Critical Quality Attributes (CQAs) and the early prediction and control of granule porosity.
- Vertical Feed Speed (VFS; rpm)
- Horizontal Feed Speed (HFS; rpm)
- Roller Compaction Force (RCF; lbs per linear inch)
- Mill Speed (MS; rpm)
Samples were taken, suspended in silicon oil and measured at-line. The measured particle distribution was studied for the initial blend and the 19 trial batches to see what process parameters really influence the particle size. Clearly, the powder blend had a smaller mean dimension compared to the granulated material and had a higher count of particles.
This Design of Experiments (DoE) data was then converted into useful information to help improve process understanding. To improve roller compaction understanding, the impact of roller compactor process parameters on the particle size distribution and other Critical Quality Attributes (CQAs) were studied in detail. The measured particle size distribution was then correlated to a downstream quality attribute (porosity) to investigate what can be used to predict and control final granule properties. The particle/parameter correlations from the Design of Experiment (DoE) data included:
- Certain process parameters have a significant impact on the particle size distribution.
- The vertical feed speed does not affect the fine particle count; the roller compaction force has a significant effect on the mean granule dimension.
- In general, vertical and horizontal feed speed did not impact particle size distribution – where as the roller compaction force and the mill speed have a significant influence. If we want to try to target a particular particle size, the roller compaction and the mill speed are two variables we can adjust to do that.
- Typically, increasing roller compaction force and/or mill speed results in an increase in the mean dimension and a decrease in the number of fines.
- A target particle size distribution can be achieved consistently by understanding the impact of process variables.
The impact of process parameters on other Critical Quality Attributes (CQAs), including ribbon thickness, granule density, and granule porosity, was also studied. Again, process parameters had significant influence on the particle distribution.
The second part of the study looked at predicting downstream quality attributes based on what was measured in situ or at-line. Granule porosity was correlated against the mean granule dimension measured during roller compaction.
BONUS: An extensive list of previous AAPS (American Association of Pharmaceutical Scientists) presentations highlighting how pharmaceutical scientists use Process Analytical Technology to further their research and optimize their manufacturing processes using Quality by Design is available. Many of these past AAPS conference presentations, including the one given by Gerald Burke of Patheon, are available for download.
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