One question that I frequently get about dissolution is what is the f2 factor and how should it be used? The f2 factor in dissolution is a similarity factor which can tell us how similar that two dissolution curves are to one another. This f2 factor is one of several of these factors, but the most commonly referred to. Most frequently, this curve is used to demonstrate the equivalence between a generic and innovator formulation, but there are other uses as well.
The f2 calculation is a comparison of two curves with at least three time points. There are some rules when using the f2 to make sure that we are getting a meaningful comparison. Variability of both of our methods should be below 20% at the first time point and under 10% for all other time points. Recent guidances also state <20% in the first 10 minutes and <10% after that. The time points selected should be reflective of the curve as well. No more than a single time point should have a value above 85% for either of the dissolution curves – this is so that we don’t bias our results high. When we do the f2 calculation we will get a value between 0 – 100, where 50 and above we consider the curves to be similar. A value of 100 would be if the two curves were an exact match. In order to use f2, n=12 of each curve should be used for comparison. Everything about the dissolution method should be identical between the two data sets except for the one thing being changed.
The most common use of the f2 is to compare two formulations. f2 is one factor used to state that a generic gives the same dissolution behavior as an innovator formulation, for example. We may also use the f2 when changing a formulation to demonstrate that there is not a change – such as a manufacturing/excipient/location change.
The f2 can also be used to assess a change to a dissolution method as well. We can test the same formulation, but change one portion of the dissolution method to make sure there isn’t a significant change as a result. Some of these changes might be evaluating different sinkers or degassing approaches for example.
f2 is one important tool for dissolution method assessment, but there are other options out there depending on the variability of your data, number of time points, and other factors.
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