An integrated material-sparing method for determining dilution potential of direct compression tablet fillers

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Direct compression (DC) tablet formulations require fillers with optimal flowability and compactibility for consistent quality.
• Understanding the "dilution potential" of a DC filler is crucial for successful manufacturability across various active pharmaceutical ingredients (APIs) and loadings.

Purpose of the Study:

• To develop and validate an integrated, material-sparing laboratory-scale method for evaluating the dilution potential of co-processed glutinous rice starch (CP-GRS).
• To assess CP-GRS's performance as a DC filler using acetaminophen (APAP) and ibuprofen (IBN) as model drugs.

Main Methods:

• An integrated laboratory-scale method was employed, focusing on tablet friability (<1% weight loss), disintegration time (<15 min), and superior flowability compared to microcrystalline cellulose.
• The critical pressure (Pc) and maximum API loading were determined for CP-GRS with granular APAP, fine APAP, and ibuprofen.

Main Results:

• Granular APAP (gAPAP) achieved up to 34% loading in CP-GRS at ~240 MPa.
• Fine APAP reached 20% loading within 143-288 MPa.
• Ibuprofen (IBN) showed a maximum API loading of 40% at 115-150 MPa.

Conclusions:

• The developed integrated method effectively evaluates the dilution potential of CP-GRS for direct compression formulations.
• This material-sparing approach facilitates efficient DC formulation development, especially in early drug development phases.