FBRM® in the Formulation Development Laboratory, A Study of Behavior During Dissolution

This study examined the feasibility of using a Lasentec^® D600L (FBRM^®  technology) to monitor formulation development processes in which the in-process particle dynamics are not well characterized or understood. The goal was to understand the effect of granulation and tableting on granule and tablet dissolution.

In the downloadable PDF, Figure 1 shows the FBRM® mean square weight statistic of two different tablet disintegrations. Tablet 1, with slow dissolution, has a larger mean particle size than Tablet 2. As expected, disintegration and breakdown of primary particles is seen. While these trends show roughly similar amounts of the coarse particle population in both tablets, Tablet 2 is weighted toward the finer end, leading to the suspicion that there may be dependence on mean particle size with dissolution rate.

In Figure 2 of the downloadable PDF, significant disintegration is not really seen. It is important to note that this process is agitating at 200 rpm, far faster than the dissolution test which agitated at 50-75 rpm. The initial and final distributions are pretty much the same for each granule type. It seems clear that the drug release is primarily by diffusion. Diffusional release will have a dependence on particle size.

In Figure 3, it looks as if agglomeration is occurring during tableting. In fact, this was found to be plastic deformation, which may have then sintered into larger particles. Fragmentation was believed to be occurring during tableting and more fines were expected in the tablet’s distribution. But it turns out the opposite is true. Again, it appears the primary release mechanism is by diffusion, not disintegration.

By showing both drug release rate dependence on granule size and increase in granule size after tableting, FBRM® proved to be a valuable tool for characterizing solid dosage formulation in the development lab.