Figure 3: Sticking profiles and representative punch-tip images for blends containing various levels of ibuprofen.
Effect of ibuprofen loading on sticking. To investigate the sensitivity of the method to various concentrations of a sticky component, different levels of ibuprofen
were mixed into a blend containing microcrystalline cellulose and 0.25% magnesium stearate. Figure 3 shows that the sticking
propensity and the powder accumulated on the punch tips during the first 100 compressions tested increased with increasing
ibuprofen concentrations. The quantitative measurements of accumulated powder were supported by visual inspection of punch
tips, which showed high degrees of surface coverage at high ibuprofen concentrations. After approximately 100 compressions,
the weight of adhered powder sometimes decreased suddenly or gradually. The sudden decreases in weight were attributed to
the detachment of large domains of adhered powder from the punch tip after further compressions. The gradual decreases were
attributed to a steady wearing of the film from the punch tip. These results highlight the unpredictable sticking behavior
of suboptimal formulations containing high levels of sticky components and emphasize the potential for challenging manufacturing
Figure 4: Tablet-sticking profile for 50% w/w spray-dried mannitol blends with various levels of magnesium stearate.
Figure 5: Tablet-sticking profile for 20% wt ibuprofen blends with various levels of magnesium stearate.
Effect of lubricant level on sticking. The effect of tableting lubricant was studied for blends containing either ibuprofen or spray-dried mannitol with various
levels of magnesium stearate. As expected from tableting experience, the spray-dried mannitol had a lower absolute sticking
propensity relative to ibuprofen. But, interestingly, opposite trends were observed for the mannitol versus the ibuprofen
formulations with various lubricant levels. For the mannitol formulations, increasing proportions of lubricant decreased sticking
(see Figure 4). This result suggests that the mannitol had a relatively high affinity for the metal punch surface, which is
reduced by lubricant. Conversely, and perhaps counterintuitively, sticking increased for ibuprofen formulations containing
high levels of lubricant (see Figure 5). This observation was previously reported using a different sticking assessment method
and attributed to the reduction in the interparticle bond strength of ibuprofen and to a eutectic formation between the ibuprofen
and magnesium stearate (1). Given these results, this method was able to indicate sticking behavior of sticky formulations
as a function of small changes in the level of tableting lubricant.
Figure 6: Sticking profiles and representative punch-tip images for blends containing various grades of mannitol and various
Effect of mannitol grade on sticking. The sticking assessment method was also tested to determine whether sticking propensity could be detected using various grades
of a single component. Figure 6 shows that after ~10 compressions, the powdered mannitol was about twice as sticky as granular
mannitol. As expected, the microcrystalline cellulose did not stick to the punch surface. The higher sticking propensity of
the powdered mannitol was hypothesized to result from its higher specific surface area, which increased its bonding potential
to itself and the punch surface. A high number of compressions was not investigated with this method because of severe die-wall
friction with the unlubricated powders. Mixing the granular mannitol at 75% w/w with microcrystalline cellulose, then further
decreasing its concentration to 50% w/w and adding 1% w/w magnesium stearate significantly decreased the sticking propensity
of the blend. This result demonstrates that the punch-sticking detection method can guide formulators when they optimize tableting-blend
compositions and before progressing to large-scale manufacturing.