Pharmacy Courses

Robustness of Dissolution Method

Robustness is a critical element of Dissolution Method Development and Validation.  Often times, robustness isn't done or doesn't consider the most important elements that could impact dissolution.  

Robustness of a method means that normal day to day variations in the lab won't result in a different profile - we want the experimental result to reflect the product's performance and not something else.  One example is this graph a customer shared with me a few years ago about the impact a small pH change had on the dissolution profile of one of their products.  This wasn't the first time I've been a dramatic change due to small pH changes.

When considering a dissolution method, you need to ensure that you have a balance between discrimination (being able to differentiate between good and bad batches) and robustness. 

Often times, I will see robustness test for small changes in RPM speed, slightly different dissolution volumes, and different systems.  When considering what to test for robustness you should consider the likelihood of that variable happening and what potential impact it could have with a slight change.  RPM is one example where variability is quite rare and I don't tend to see a lot of difference between results within acceptable RPM ranges (48-52 RPM for example).

So, what are some good areas to look at for robustness?  pH is one critical area as it is both likely to change and can have large impacts.  Surfactant concentration, buffer strength, and other changes in the media may also be worth looking into. 

I would also strongly recommend use of qualified dissolution systems in the lab that are as different as possible as well as chemists with varying skills.  Having a newly trained dissolution chemist run the product on the oldest unit in the lab and compare that to an expert chemist on a newer unit can tease out a lot of potential issues for example.  

You may also want to consider making purposeful changes in centering and paddle/basket height as these can have great impacts in the hydrodynamics in the vessel.  Setting a paddle at 24mm and 26mm for example would be a potential experiment to try.

Challenging your method well with robustness studies will save you from countless issues with later failure investigations, method transfer issues, etc. in the future.

Related: Dissolution Method Development and Media Selection for a New Dosage Form

Resource Person: Ken Boda (Dissolution Product Specialist at Agilent Technologies)

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