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

Protective particles. Protective particles, also known as cushioning agents, help prevent damage to the drug–polymer-loaded core pellets. Protective particles rearrange themselves between the pellets and reduce the void space to prevent direct contact of pellets after the application of compression pressure. Preferred excipients are agglomerates (e.g., pellets or granules) that lower the risk that pellets will separate by size or density during processing, thus leading to weight variation or dose nonuniformity. When used as cushioning agents, primary particles (e.g., powder) give rise to the above problems (16, 21, 31). The cushioning effect of an excipient depends on its particle size, volume, and compaction properties. The method by which the particles undergo volume reduction needs to be studied. Several studies proved MCC and polyethylene glycol to be good excipients for compaction because of their plastic deformation (22, 32–34). Studies also proved that lactose, which undergoes fragmentation upon compression, offers better protection than MCC (35).

However, studies of 14 excipients proved that excipients that show good plastic deformation during compression give the best protection to the coating material (36). Particle size is an important factor in preformulation, and some studies suggested that particles smaller than 20 μm prevent damage to the coating. Increased dissolution rate was observed with particles bigger than 20 μm (29, 37). Using wax as a cushioning agent during pellet compression also is of great help to the formulator because it prevents damage to the coating during compression (38).

Nature of polymer. Polymers play an important part in any controlled- or modified-release dosage form. The final release of the drug from the formulation depends on the polymer used. A polymer must have appropriate plastic and elastic properties to withstand the shear of compression and compaction. Various polymers currently used to modify the release of pellets are either cellulosic polymers (e.g., ethyl cellulose) or acrylic polymers (e.g., Divakar's Polex, Evonik's Eudragit, or BASF's Kollicoat). The most frequently used polymers to extend the release of water-insoluble drugs are ethyl cellulose and ammonio methacrylate copolymers (39). Film-forming polymers have satisfactory elastic properties that prevent the rupture of the coating polymer, and good plastic properties that prevent deformation during compression.

Studies revealed that not only does the coating material affect compression properties, but also the solution in which polymer is dispersed or dissolved. The process entails dispersing polymer in water as pseudolatex or dissol-ving the polymer in an organic solvent. Investigations were conducted on ethyl cellulose to study its sustained-release properties after coating and compression in tablets. Ethyl cellulose improved pellets' puncture strength and elongation by making them brittle. The mechanical properties of ethyl cellulose were less affected after it was plasticized with pseudolatexes (19). Beads composed of alternating layers of ethyl cellulose, drug, and cushioning agent are less brittle than those that include only drug and ethyl cellulose.

Chang and Rudnic found that the solvent-based coatings were affected less by compression than the aqueous-based coatings were. Solvent-based coatings improved flexibility and mechanical stability in comparison with aqueous-based coatings (40). The coated pellets ruptured on compression, which affects the film formed on the pellets' surface.

To minimize or overcome rupture during compression, Bodmeier suggested placing the compressed pellets in a hot-air oven above their glass-transition temperature (5). The brittle and elastic properties of MCC pellets were modified by applying a water-based ethyl cellulose coating to them. Thus, plastoelastic properties were introduced to the pellets after coating, which improved their deformation characteristics (31).

Bechard and Celik showed that aqueous dispersions of ethyl cellulose for compression into multiunit tablets can, however, lead to coating failure through the formation of cracks and flaws (31–32). Films formed with high elasticity and apparent Newtonian viscosity delivered the maximum protection to the pellet core and coating on compaction (16). Lehmann suggested that the coating should be elongated at least 75% at the break to prevent the coating from rupturing during compression (41).


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