Dear GMP colleagues,
I have a question about how to increase tablet hardness without affecting other critical parameters of the tablets. Our problem at the moment is that our CMO in Asia produced the domperidone tablets within the specifications [40-120N], i.e. 50-60N. But when the tablets are tested in an EU-Lab, the result is often round 35N, which means an OOS. We have investigated this problem, but no root cause could be observed. Perhaps there are people in this group who can give me advise how to increase the hardness to a min. of 80N for example? The CMO is not very cooperative in this case as the tablets are within the spec in their site.
Many thanks in advance for your help.
Thanks for the query!
Several factors influence the hardness of tablets including but not limited to the composition of formulation (ingredients), type of binder used, binder fluid temperature, moisture content (%w/w), and morphology of the granules. Most of the Domperidone formulations available in the market are formulated using wet granulation approach with Povidone/maize starch as the binder.
It will be helpful to support you if you can give more details of your Domperidone formulation:
You mentioned that the tablet hardness when tested at the CMO (in Asia) was 50-60N but the same batch of tablets showed lower hardness i.e., about 35N when tested in the EU. The probable root cause for reduced hardness over time is due to elevated humidity levels which may be attributed to the absorption of moisture into the tablets causing bond disruption and loss in tablet strength. In some cases loss of moisture could also account for reduction in tablet hardness over time or on storage. I recommend you to check the moisture content of the tablets at the CMO (in Asia) and compare it against the moisture content of the batches on arrival in the EU? This may help.
We can increase tablet hardness by controlling the critical process parameters (for example, increasing the compression force and reducing rotation speed) and critical quality attributes (for example, reducing the tablet thickness.
As I mentioned earlier, I can be of help if you can give more details of your issue(s).
Dr. Shashi Rudrangi
Domperidone is BSC Class II drug (low solubility), hence increasing hardness at the CMOs site during tableting comes with a risk of affecting the disintegration/dissolution.
Changes in environmental conditions during the transport or between laboratories (assuming the testing method is identical) might be my next look-into.
I’ve seen tablet hardness both dramatically increasing and decreasing after a short exposure to the lab environment, so cbetter containment might prove/disprove this hypothesis.
Just my thoughts given the shared information. Forgive me if I am stating the obvious in case you’ve looked into these things.
Hi all thanks for your advices…glad to hear that the measures that we take are also advised by you. We have asked the CMO to lower the speed and the compaction force of the compression machine.
We will see if those measures will solve the problem. If not we will try another measures mentioned in your answers.
By reducing the thickness, hardness of the tablet can be increased.
Addition of moisture means water at blending stage and perform in house design LOD limit for bulk product then have a trial on 1kg compress it and then results might be on increased hardness with not affecting other critical parameters.