Hydrophilic Lubricants in Pharmaceutical Solid Dosage Forms: Mechanisms, Current Applications, and Future Perspectives

Lubricants are critical excipients in the production of solid pharmaceutical dosage forms, directly influencing powder flow, compaction behavior, and tablet quality. Magnesium stearate (MgSt) is widely used owing to its excellent lubrication efficiency. However, its hydrophobic surface coverage and sensitivity to shear conditions can severely reduce inter-particulate bonding. Consequently, this adversely affects tablet wetting, disintegration, and drug release, particularly under over-lubrication conditions. For this reason, hydrophilic, amphiphilic, and less hydrophobic alternative lubricant materials have gained increasing attention. In this review, these lubricants with hydrophilic, amphiphilic, or low-hydrophobicity properties are collectively referred to as “hydrophilic lubricants”, and mainly include polyethylene glycol (PEG), sodium lauryl sulfate (SLS), poloxamers, and sodium stearyl fumarate (SSF). This narrative review summarizes the physicochemical characteristics, lubrication mechanisms, formulation applications, and effects on tablet mechanical properties, disintegration, and drug release of these alternative lubricants, and discusses the influence of lubricant properties, concentration, specific surface area, and incorporation method on lubrication performance. Furthermore, this review focuses on lubrication issues in continuous manufacturing and discusses the prospects of process analytical technology and predictive modeling. However, the available evidence remains predominantly derived from MgSt-based systems, and whether the relevant conclusions can be extrapolated to hydrophilic lubricants has not yet been validated. Nevertheless, these approaches hold promise for linking the distribution of hydrophilic lubricants and process conditions to tablet critical quality attributes, thereby providing a more rational control strategy for the lubrication process.