Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles

Abstract

Oral modified-release multiparticulate dosage forms, which are also referred to as oral multiple-unit particulate systems, are becoming increasingly popular for oral drug delivery applications. The compaction of polymer-coated multiparticulates into tablets to produce a sustained-release dosage form is preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a promising solution to chronic conditions, patients' adherence, and swallowing difficulties if incorporated into orodispersible matrices. Nonetheless, the compaction of multiparticulates often damages the functional polymer coat, which results in a rapid release of the drug substance and the subsequent loss of sustained-release properties. This review brings to the forefront key formulation variables that are likely to influence the compaction of coated multiparticulates into sustained-release tablets. It focusses on the tabletting of coated drug-loaded pellets, microparticles, and nanoparticles with a designated section on each. Furthermore, it explores the various approaches that are used to evaluate the compaction behaviour of particulate systems.

Keywords: compaction; multiparticulate; nano/microparticles; pellets; polymers.

Figure 1

Diagram showing how drug-loaded pellets are prepared using an extrusion spheronization technique.

Figure 2

Schematic representation of tablet comprising of coated pellets.

Figure 3

Microparticles (microspheres and microcapsules) matrix and reservoir systems.

Figure 4

Drug-loaded coated nanospheres/nanocapsules.

Figure 5

Heckel profile represents the relationship between porosity and applied pressure: the first part (1) is particle rearrangements and fragmentation, the second part (2) is the elastic and plastic deformation, and the third part (3) is the effect of elastic deformation.

Figure 6

The illustration of the strain pressure curve, in which C represents volume reduction, and P is the applied pressure; a and b are constants according to Kawakita model.