Co-Processing Acetaminophen with Nanocellulose to Enhance Tabletability

Abstract

Nanocellulose, a sub-micron cellulose powder, was investigated as a potential filler excipient to enhance the tabletability of acetaminophen (APAP). Due to its high specific surface area, nanocellulose was expected to outperform the tabletability enhancement provided by microcrystalline cellulose (MCC), a common tablet filler used in pharmaceutical tablets. Results showed that nanocellulose is inferior to MCC when used as a conventional filler. This is due to the difficulty in deaggregating and dispersing aggregates of nanocellulose using a typical dry blending process.

Highlights

Nanocellulose, due to its high specific surface area, was investigated as a tablet filler used to enhance tabletability.

Nanocellulose is shown to be a poor tablet filler in comparison to microcrystalline cellulose when used conventionally in a dry blending process.

To improve its effectiveness, nanocellulose is blended or “co-processed” as a suspension using a twin-screw process.

Significant improvement to acetaminophen, a model poorly compacting pharmaceutical active, was obtained at only 1.10 % w/w nanocellulose.

Such remarkable improvement allowed acetaminophen to be processed into a tablet without any addition filler.

To improve its effectiveness, nanocellulose prepared as a suspension was blended or “co-processed” with APAP using a twin-screw process. Microscopy images show that the twin-screw process coats the APAP with nanocellulose. The tabletability of APAP was significantly improved by low concentrations of nanocellulose up to 1.10% w/w. Such remarkable improvement allowed acetaminophen to be processed into tablets without any additional excipients. This study shows that nanocellulose can be used as a highly functional additive to enhance tabletability at low concentrations.

Materials

Acetaminophen (APAP), a crystalline API, was purchased from Spectrum Chemical Manufacturing Corp. Nanocellulose (Cellulose Nanocrystal), a sub-micron cellulose powder, was purchased from Nanografi. The manufacturer states that this grade of nanocellulose has a particle diameter of 10-20 nm and a length of 300-900 nm. Microcrystalline cellulose (Avicel PH 102) was purchased from DuPont. Cab-O-Sil M5P nano-sized silicon dioxide was purchased from Cabot Corporation and used as a glidant.

Maxx Capece, Co-Processing Acetaminophen with Nanocellulose to Enhance Tabletability, Journal of Pharmaceutical Sciences, 2025, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2025.02.004.