- The main method of ascertaining the progress of the granulation process is by monitoring the energy used, (through time, amps, kW, or torque) during the wet granulation phase.
- Additional useful information can be obtained by looking at what is happening to the product at each phase of the process and by evaluating the residual product in the granulator bowl at the end of the batch.
- To achieve this, the process should be interrupted at the completion of each stage of the granulation process and the lid of the vessel opened to enable product inspection.
For example:
- After the completion of the “Dry mixing” stage interrupt the process and open the lid of the granulator bowl.
- Inspect the underside of the lid for evidence of residual powders impinged on it. If present, this would indicate that the fill volume is too high and/or the impeller speed is too fast.
- Look at the surface of the powder bed. If small agglomerations have formed, this would indicate that the impeller speed is too low, (see the below image).
- If the product has aerated during the dry mixing phase, the product fill volume will have increased. In extreme cases, it can exceed the maximum fill volume, where it would negatively impact on the mixing efficiency and on the spraying area /coverage during the binder addition.
- Changes in the bulk densities of the ingredients can have a similar impact, which is one of the reasons why raw ingredients have specified limits with which they must comply.
- If the binder is sprayed into the granulator bowl and the product volume has changed, the spray area/coverage will differ.
For example:
- if the fill volume has increased, the spray area will have decreased (see the image on the left in the below image). As a fixed rate of addition of the binder is sprayed over a much smaller area, it would lead to localized over-wetting of the product and the formation of lumps.
- After the completion of the “Binder addition” phase, interrupt the process and open the lid of the granulator bowl.
- Look at the product fill volume within the granulator bowl. The volume should have reduced substantially, (see below image) as the ingredients would have started to densify.
- There shouldn’t be any visible signs of over-wet product or signs of the binder adhering to the side wall of the granulator bowl.
- After the completion of the “Wet massing” phase, interrupt the process and open the lid of the granulator bowl.
- Look at the product fill volume within the granulator bowl. This volume should have decreased even further. In some cases though, the volume may have increased due to the uptake of liquid by certain excipients (e.g. microcrystalline cellulose or starch maize and water).
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- Using the correct PPE, take a handful of products and evaluate the distribution of the binder and the formation of the granule particles, (see the below image).
- Check that there are no signs of the product starting to develop into “golf balls”, (see below image), this is an indication that the product is close to over granulating.
- After completion of the “Discharge” phase, stop the process and open the lid of the granulator bowl.
- Inspect the inner surfaces of the granulator bowl, (see below Image).
- Signs of excess residual product on the side wall of the granulator bowl would indicate that either the impeller speed is too fast during the wet massing phase, the moisture content of the product is too high and the need to look into the various binder properties such as, viscosity, quantity and rate of addition.
- Signs of excess residual product on the base of the granulator bowl would indicate that the binder is not being spread out sufficiently to be incorporated into the mix. Usually, if a dense binder (e.g. starch paste) is being used it can easily make its’ way through a slow-moving powder bed, resulting in the binder being smeared onto the base of the granulator bowl. Increasing the impeller speed would help to prevent this occurrence.
- Signs of excess product on the center cone of the impeller would indicate that either the binder addition position is incorrect, (needs to be at a point approximately two-thirds of the radius of the impeller blade) or that the helicoidal action is bringing the binder back onto the cone of the impeller and that the binder properties need to be investigated.
- Inspect the chopper blades to see if they are clear or clogged with excess product, (see below image). Clogged chopper blades restrict the path of the product as it moves around the product bowl during the wet massing phase. This can result in an over-granulated product.
- Residual product adhering to the granulator bowl indicates that the process has not been optimized and an intervention is required.
- Rectifying the various issues mentioned will help increase the product yield and will also create a more uniform dense granule that is required for good tableting.
- A similar approach can be used on all of the other processing equipment to establish whether the process is running optimally or not, for example by visually inspecting the inner surface of the drum of a tablet coater to see if there are areas of the excess over-spray, which would indicate a problem with a particular spray gun.
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