Scientific papers
The tabletability flip phenomenon (TFP)—where an active pharmaceutical ingredient (API) with inferior intrinsic tabletability demonstrates improved tabletability when combined with excipients—is well established in direct compression formulations. However, its behavior in granulated systems has not been previously investigated. This study aims to examine the presence of TFP in dry-granulated formulations and to elucidate the mechanisms governing this behavior.
Acetaminophen (APAP) and ibuprofen (IBU), two APIs known to exhibit TFP in non-granulated blends, were selected as model compounds. Granules of each API were produced at two target porosities (9% and 19%) by adjusting compaction pressure. Tabletability, bonding area (BA), and bonding strength (BS) were evaluated for granules both with and without varying amounts of extragranular magnesium stearate (MgSt).
Granules with higher porosity (19%) underwent substantial fragmentation during compaction, preserving TFP via mechanisms similar to those observed in pre-blend systems. In contrast, low-porosity granules (9%) exhibited limited fragmentation, causing tabletability to be primarily dictated by intrinsic material properties influencing the BA–BS relationship. Although APAP granules formed smaller BA due to reduced deformability, their higher BS resulted in superior tabletability, thereby sustaining TFP. The addition of ≥ 1% MgSt reduced differences in BS between formulations, suppressing TFP as the more deformable IBU granules achieved higher tabletability through increased BA.
This study confirms the relevance of the BA–BS framework for interpreting TFP in dry-granulated systems and underscores the critical role of granule porosity and lubricant concentration in controlling tabletability during dry granulation.
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