Effects of crystalline form on the tableting compression mechanism of phenobarbital polymorphs

The effects of the polymorphic form on the compression mechanism of forms A, B, and F of phenobarbital were investigated using a compression simulator, mercury porosimetry, X-ray diffraction analysis, BET gas absorption method, and scanning electron microscopic (SEM) photography. The order of tablet hardness obtained from all phenobarbital polymorphs was form A > form B > form F in accordance with that of the specific surface area. The Cooper and Eaton method was applied to evaluate two individual compression processes: particle rearrangement (phase I) and fragmentation and/or deformation (phase II). The parameters for compression processes were calculated using a nonlinear regression analyses program, and the compression energies of phases I and II were calculated from these parameters. The relationship between specific surface area after compression and compression energy at phase I showed a good linear correlation, but their ratio did not. In contrast, the specific surface area ratio showed a linear relationship with the compression energy on phase II, but again the ratio of these two parameters did not. The tablet hardness showed a linear relationship with the specific surface area ratio, but not with the specific surface area. Again, the ratio of these two parameters did not show a linear relationship.