Effect of Lubricants and Lubrication Time on the Release of Granules for Compaction: A Comprehensive Review of Mechanisms, Formulation Variables and Evaluation

Lubricants are indispensable yet paradoxical excipients in tablet manufacture: present at concentrations of only a fraction of a percent to a few percent, they reduce die-wall friction, prevent sticking and improve granule flow, but the very surface activity that makes them effective can also impair the mechanical strength, disintegration and dissolution of the finished tablet. This review examines how the type of lubricant and the duration of lubrication (mixing) time together govern the compaction behaviour and drug-release performance of granules, taking paracetamol—a poorly compressible, poorly flowing model drug manufactured almost exclusively by wet granulation—as the reference system. Five representative lubricants are compared: the hydrophobic stearates (stearic acid, magnesium stearate and zinc stearate) and the more hydrophilic sodium benzoate and polyethylene glycol. The mechanism of boundary lubrication, the well-documented “magnesium stearate effect” and the phenomenon of over-lubrication on prolonged mixing are discussed in detail, alongside the influence of lubricant type and lubrication time on granule flowability (Carr's index and Hausner ratio), tablet hardness, disintegration time and in-vitro dissolution and its kinetics. Illustrative analytical data, a complete evaluation framework and current market context are presented graphically. Hydrophilic lubricants and shorter, well-controlled lubrication times generally favour faster release, whereas hydrophobic stearates and prolonged mixing slow disintegration and dissolution; the central conclusion is that lubricant selection and lubrication time must be jointly optimised—ideally through a statistically designed approach—to balance manufacturability against drug release.