Salako conducted a similar study of pellets' deformability and tensile strength using MCC-based beads loaded with theophylline, which are hard. Soft pellets were prepared with glyceryl monostearate (15).

Pellets undergo structural modifications during compaction. They need elasticity and flexibility to withstand compaction pressure. The ideal pellets are strong, not brittle, and have a low elastic resilience. They should deform under load application and load recovery without fracture (16). Knowledge of the compression behavior of uncoated pellets can provide a basis for the manufacture of multiunit tablets from barrier-coated pellets without damaging their coating.

Size and shape. Pellets undergo deformation after compression. Hence, the size of the pellets affects their compaction properties and the drug release from compacted pellets. Large pellets tend to undergo deformation more readily than small ones. Small pellets are stronger than large ones; they withstand compression pressure with less deformation (17). The strength of the pellets affects the final strength of the compressed tablet and helps ensure the desired release rate.

In addition to size, the shape of pellets affects the compression behavior and tablet-forming ability of granular materials. Irregular shapes induce complex compression behavior in granules. They increase the attrition of the granules, thus resulting in increased deformation (19–20). Flament found that, after the application of similar quantities of coating on pellets, small pellets were more fragile than large pellets. The probable reason is that small pellets' increased surface area reduced the film-coating thickness (21). Furthermore, increases in particle size resulted in more damage to the coating, as indicated by larger differences between the release profiles of tablets and uncompressed pellets (20).

Beckert compacted coated pellets of two crushing strengths with different excipients and concluded that the harder pellets were better able to withstand compression forces because they deformed to a lesser degree and their film coatings were less susceptible to rupture (22). Ragnarsson found that the compaction of small pellets had less effect on drug release than the compaction of large pellets. He also concluded, however, that the effect of pellet size depended on the choice of coating material, as well as on the amount and properties of the pellets and the excipients forming the tablet (23).

Density and porosity. Pellet density and size play an important role in achieving content and weight uniformity. Because of their intragranular porosity, pellets tend to densify. By modifying their intragranular porosity, manufacturers can deform and densify pellets during compression (24–27). Pellets with a narrow size distribution and excipients of similar sizes, shapes, and densities can prevent segregation (28). The critical density for achieving prolonged gastric residence may be between 2.4 and 2.8 g/cm³ (29). The amount and choice of material used for binding or granulating the powders during pelletization, and the compaction pressure, have a direct effect on the porosity.

Unlubricated pellets also require higher pressures than lubricated pellets (5). A study by Bodmeier revealed that an increased proportion of water as granulating fluid in the mixture led to hard and less porous tablets with a slow drug-release pattern. Similarly, pellets prepared using 95% ethanol as a granulating fluid showed good compressibility in contrast with pellets prepared with water (5). Using 95% ethanol during granulation formed strong intergranular bonds with an increased porosity, which finally increased the deformation of the formed pellets during compaction into tablets.

Porosity also can affect drug release. Tuton showed that pellets of high porosity were densely packed and deformed, and that the drug release from these pellets was not affected. But upon compaction of pellets with low porosity, the pellets were compressed with slight densification and deformation, leading to increased drug release. Using highly porous pellets did not alter the drug release after compression, in comparison with pellets with low porosity (30).

Compression force. Compression force is a critical parameter that must be optimized during tableting of pellets. Several studies investigated the compression force required for compressing pellets and found that 15 KN was sufficient for tablets with smooth surfaces. Flament studied the compression of theophylline-loaded pellets with acrylic polymer. Upon the application of compression pressure, the pellets were compacted by deformation at 6 KN. Further investigation revealed that increasing the compaction force to 20 KN did not alter the dissolution rate significantly (21).