Mini review: Mechanisms to the loss of tabletability by dry granulation

In this mini-review, we have critically examined literature aimed at understanding the mechanisms to the frequently observed phenomenon of loss of tabletability of a powder after dry granulation by slugging or roll compaction. Impact of each mechanism on tabletability could be explained by considering their influence on either bonding area (BA) or bonding strength (BS). For plastically deforming materials, key mechanisms that influence tabletability of dry granulated powders include lubrication, granule size enlargement, and granule hardening. The use of more lubricant leads to lower BS and reduced tabletability. Compared to external lubrication, internal lubrication tends to exhibit more detrimental effects on tabletability. If extensive fragmentation can be avoided, granules with a higher porosity (or lower solid fraction) are more deformable under compaction pressure to favor larger BA and stronger tablet. For brittle materials, granule hardening can still be important despite they are relatively less prone to the lubrication problem. Not surprisingly, there is not a single mechanism that can explain all observations. The dominating mechanism in each specific case depends on material properties and process parameters. We have summarized a total of eight important aspects that should be addressed when developing a dry granulation (DG) process. We have also presented four golden rules to be considered when dealing with the dry granulation process.