One of the most common myths analysts come to me with is that coning is always a problem to be overcome in the lab. Not only is coning not always a problem – but sometimes it can give you a wealth of information about your dissolution. So, let’s discuss coning. Why does it happen? How can it be useful? When is it a problem – and how can you address it?
Coning is to be expected for formulations that are disintegrating or contain powders or beads. The mixing in the vessel is weakest in the bottom center of the dissolution vessel. The lower mixing and our product sinking means that we will have our product settle there and form a cone shape.
If you have a cone which has some movement and is not tightly compacted, then this can be an excellent opportunity to see how your dissolution is performing. Cone size and shape generally correlate very closely with your dissolution results, so you can use this to make an educated guess about how the dissolution is going so far. If you’re seeing that the cones are all relatively the same size and shape, that means you should have a consistent dissolution as well. If you see that you have a cone or cones of different sizes, then this likely indicates your results will be variable. If you see this identify which cones are different and look for any potential trends. Some examples:
- If you see a single cone that is smaller, this might indicate a problem with that sample or could point to an alignment issue in that position. Does the paddle appear to be the same height? Do we see greater wobble in this position?
- If you see that all of the cones are different sizes, then we may have either a variable formulation itself or a variable dissolution set up. I’ve seen variable dissolution set ups happening when using low quality consumables, especially vessels.
- If you see that cones follow a trend in the bath from left to right or front to back, then this can indicate an overall alignment issue with the bath itself such as a head leaning to one side.
If you see that you have a rigid cone and have low/incomplete results when you’re developing a new dissolution method, then we may want to consider options to overcome those challenges. A rigid cone generally means that once your product has disintegrated and some dissolution has occurred, you are left with a heavy blanket of excipients on top of the remaining product. This excipient layer then can shield your drug from the media and slows or stops dissolution. If you see this in method/formulation development, you may want to consider:
- Increasing the RPM speed
- Using an Apex (also known as Peak) vessel
- Explore Apparatus 3
- Discuss formulation modifications, if possible
Keep in mind that increasing agitation in your dissolution comes with the risk of losing discriminatory power. We never want to turn dissolution into a blender.
Related Topics:
| Non-Sink Conditions | List of Regulatory Authorities | Marketing Authorization Dossiers |
| Bioavailability | Biotechnology | Bioinformatics |
Resource Person: Ken Boda