Applying the approach of so-called “dry-coating” techniques commonly used for glidants, dry powder processing was explored as a method to coat the active with nanocellulose. Diffusive blending, co-milling, and acoustic mixing were all shown to be ineffective. This is due to the difficulty in deaggregating and dispersing aggregates of nanocellulose using these dry processes. Wet processing techniques, twin-screw and fluid-bed coating, are detailed which were more effective at dispersing and coating nanocellulose. In one such example, the tabletability of acetaminophen was significantly improved by low concentrations of nanocellulose up to 2.0% w/w. A 2.0% w/w coating increased tablet tensile strength by nearly 200%. With respect to tablet formulation, it was found that APAP coated with 2.0% w/w nanocellulose allowed a 60% reduction in filler to produce tablets acceptable for manufacturing compared to APAP without nanocellulose. Such remarkable improvement also allowed acetaminophen, a poorly compactable active, to be processed into tablets without any additional excipients.
The effectiveness of nanocellulose at low concentrations is somewhat analogous to the benefit of adding small amounts (≤ 1% w/w) of nano-sized silicon dioxide (i.e. glidant) to enhance powder flowability. As shown in this study, the use of nanocellulose as a highly functional additive to enhance tabletability may allow substantial improvement in formulation and process development for tablet drug products.