Impact of particle size distribution on the degree of compaction and mechanical properties of pharmaceutical tablets: Current perspectives and future trends

The size of constituent particles, together with the breadth of their distribution, is among the most influential material attributes governing how a pharmaceutical powder consolidates into a tablet and how that tablet subsequently performs. Particle dimensions shape powder flow, the efficiency with which a powder bed packs, the residual porosity of the compact and, ultimately, its tensile strength and tendency to recover elastically. Because finer fractions present a greater specific surface area, they tend to form more numerous interparticle contacts and stronger compacts, although powders that are too fine flow poorly and complicate downstream handling. The particle size distribution has been linked to densification rate, mean yield pressure and the strength developed at a given compression pressure. Classical density-pressure relationships, notably the Heckel and Kawakita treatments, remain the standard means of interrogating these mechanisms, while porosity has emerged as a unifying property connecting compaction to disintegration and dissolution. The maturation of Quality by Design, process analytical technology, discrete-element simulation and non-destructive terahertz sensing has sharpened the understanding of size-dependent compaction. This review surveys the fundamentals of particle size and its distribution, methods of particle size analysis, the mechanisms of tablet compaction, the principal compression models, the influence of particle size on powder and tablet properties, industrial applications, enabling technologies, persistent challenges and future directions. A clear understanding of how particle size and the degree of compaction interact remains central to developing robust tablet formulations with consistent mechanical properties and predictable drug release.