Distribution pattern and surface nature-mediated differential effects of hydrophilic and hydrophobic nano-silica on key direct compaction properties of Citri Reticulatae Pericarpium powder by co-processing

This work aims to improve direct compaction properties of Citri Reticulatae Pericarpium powder (CB) by liquid dispersion co-processing with hydrophilic or hydrophobic nano-silica (INS or ONS). Such wet co-processing was applied to evenly distribute NS to CB. Typically, INS achieved up to 13.8-fold improvement in CB tabletability by affecting both bonding area and bonding strength. In comparison, ONS did better in improving flowability (angle of repose from 35.6° to 27.8°) and achieved up to 4.2-fold improvement in tabletability. Moreover, the bulk density of CB-NS was increased to ~0.65 g/mL at the ratio of 10:1. There was generally a bell-shaped relationship between improvements and CB/NS ratios, especially for ONS. The different distribution pattern and surface nature of INS and ONS caused by polarity difference were the key reasons for their different effects. Compared to the traditional MCC-based formulation strategy, qualified tablets with 3-fold higher CB loading (91.0%) were achieved. [Display omitted] •Different distribution patterns of nano-silica (NS) result in different effects.•NS has various effects in different use levels and/or adding methods.•NS improves multiple properties of CB and achieves the qualitative changes.•NS-modifying can leave more room for increasing drug loading of herbal powders.