Multiunit Particulate Systems: A Current Drug-Delivery Technology - Pharmaceutical Technology

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Multiunit Particulate Systems: A Current Drug-Delivery Technology
The current review describes the role and selection of excipients, pellet core, coating materials, and compression with various cushioning agents.


Pharmaceutical Technology
Volume 35, Issue 7, pp. 60-66

Compressibility and compactibility

The ability of a powder to decrease in volume under pressure is called compressibility, and the ability of the powdered material to be compressed into a tablet of specific strength is called compactability (7). According to one theory, the compaction sequence for elastic materials includes particle rearrangement, plastic deformation, and elastic deformation (8). In Van der Zwan and Siskens's theory of the compaction of pellets, the process of volume reduction involves the filling of interparticle voids, where the secondary particles undergo readjustment; the fragmentation and plastic deformation of secondary particles; the filling of intraparticular voids, where primary particles rearrange, making the mass more dense; and the fragmentation and plastic deformation of the primary particles (9).

In an entirely different theory of compaction and volume reduction, Johansson stated that the secondary particles rearrange to fill interparticle voids where the strength of the compressed powder is too low due to low bonding force. Next, the surfaces of the secondary particles are flattened with local deformation. Then, as secondary particles undergo bulk deformation, they simultaneously become densely packed, and bonding strength increases significantly. Finally, low inter- and intragranular porosity causes the compression process to stop with less volume reduction of the bed but with higher bonding within the particles (10).

The major challenge of a formulator is to retain pelletproperties after the compaction process. To aid formulators, this article will describe the factors involved in the compaction and consolidation of coated and uncoated pellets.

Compression of coated pellets

Preparing compacted MUPS (i.e., compressing coated pellets to achieve multiple objectives) is a challenging task. During compaction, the polymeric coating may not withstand the compression force, thus affecting the surface of polymer and the pellets, which could cause the drug to be released in an undesired manner.

Hence, thorough process optimization is needed for the compaction of coated pellets. The main variables involved are the compression force and the velocity of the punches. The hardness, thickness, and porosity of the tablets must be maintained. Other important factors concerning the preparation of multiunit tablets are the properties of the barrier coating and the inclusion of protective excipient particles in the tablet formulation, and these parameters have been investigated extensively.

Pellet core. Many formulators have successfully studied and investigated the compression behavior of pellets consisting of various excipients. The selection and study of the material used to manufacture pellets is important to achieve the desired release pattern (11). The comparison between soft and hard pellets revealed that the pellets with soft constituents had the greater chance that intergranular pore spaces would be filled because the primary particles can move within the agglomerate. Harder pellets tend to fail at the surface because of the pressure of compaction.

Nicklasson studied the behavior of microcrystalline cellulose (MCC), alone and in combination with polyethylene glycol and dicalcium phosphate pellets, during and after compression. He concluded that pellets are deformed after compression, depending on their capacity for, mode of, and resistance to deformation. Nicklasson also studied polyethylene glycol as a cushioning agent to analyze the compression behavior of pellets. For the study, he used MCC-based beads loaded with theophylline, which are hard, and softer beads prepared with glyceryl monostearate (12).

Wang attempted to study the compression of lactose and MCC in various concentrations of powder and pellets. MCC-based pellets lost their plasticity during granulation and hence showed poor compactability, compared with lactose-based pellets (13). Iloanusi and Schwartz studied the crucial role that plastic deformation plays in compression by adding wax to the MCC bead formulations. Pellets with wax as a cushioning agent had more compressibility than beads without wax as a compression modifier (14).

Salako confirmed the advantages of softening materials during compression. On application of initial compaction pressure, the soft beads ruptured. On further application of pressure, the beads deformed and formed a network. Because of the soft nature of the beads, the material readily underwent deformation and rearrangement. Harder pellets are compact, and upon the application of compaction pressure, they underwent reduction in volume by particle rearrangement, not because of bond formation, compared with soft pellets (15).


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