Tabletability Flip in Dry Granulated Systems

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• The tabletability flip phenomenon (TFP) is observed in direct compression, where less deformable active pharmaceutical ingredients (APIs) show improved tabletability with excipients.
• The influence of granulation, specifically dry granulation, on TFP remains largely uncharacterized, necessitating further investigation.

Purpose of the Study:

• To explore the occurrence and underlying mechanisms of TFP in dry-granulated formulations.
• To evaluate the impact of granule porosity and magnesium stearate (MgSt) content on TFP.

Main Methods:

• Acetaminophen (APAP) and ibuprofen (IBU) were used as model APIs for dry granulation.
• Granules were prepared at two porosity levels (9% and 19%) by adjusting compaction pressure.
• Tabletability, bonding area (BA), and bonding strength (BS) were assessed with varying extragranular MgSt concentrations.

Main Results:

• Higher porosity granules (19%) exhibited TFP via fragmentation, similar to non-granulated blends.
• Lower porosity granules (9%) showed TFP governed by the interplay of BA and BS, with APAP maintaining TFP due to higher BS despite lower BA.
• Incorporating ≥1% MgSt reduced BS differences, eliminating TFP by favoring the higher tabletability of softer IBU granules.

Conclusions:

• The bonding area-bonding strength (BA-BS) framework effectively explains TFP in granulated systems.
• Controlling granule porosity and MgSt levels is crucial for optimizing tabletability in dry granulation.
• Understanding these factors is key to predicting and managing TFP in pharmaceutical manufacturing.