The Hour of the Particle - Pharmaceutical Technology

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The Hour of the Particle
Is now the time for multiparticulates to shine as a controlled-release solution?


Pharmaceutical Technology
Volume 34, Issue 7, pp. 38-42

Multiparticulates' advantages

Multiparticulates' size enables them to provide "considerable clinical advantages," says Gurvinder Singh Rekhi, senior director of oral controlled release at Elan Drug Technologies (Gainesville, GA) and member of the Pharmaceutical Technology editorial board. Because the dose is divided into many subunits, multiparticulates have a much lower risk of dose dumping than tablets do. And single doses that are released accidentally (e.g., by fat) may cause higher incidence of adverse events, compared with multiple units, says Singh.

Dividing a dose into many multiparticulates helps distribute the drug slowly, evenly, and consistently. At any given time, multiparticulates are present in the stomach, the intestine, and other sites in the GI tract, which helps maximize drug absorption. Because multiparticulates provide smooth transit through the GI tract and are less dependent on gastric emptying, they greatly reduce the variability between patients' plasma profiles. Also, multiparticulates' size limits the exposure of the drug to the epithelium and reduces the possibility of irritating the GI tract and the bowel, says Castan.

In addition, multiparticulates can allow drugmakers to provide patients with individualized dosing. For example, a company could package the pellets in a device that patients press to dispense individualized doses. A patient thus could take the appropriate dose for his or her weight or age group. And a dosage form that included instant- and extended-release multiparticulates could improve compliance by reducing the number of doses the patient must take each day.

Multiparticulates can be used to improve convenience and patient compliance, too. For example, a manufacturer might choose to develop a formulation as a traditional tablet because it would allow the company to reach the patient relatively quickly. Afterward, the manufacturer could develop a multiparticulate dosage form of the same drug to provide modified release for increased bioavailability or once-daily application.

In addition, multiparticulates have various advantages for pharmaceutical companies. For instance, drugmakers can combine APIs that otherwise would be chemically incompatible by creating multiparticulates of various formulations and encapsulating them. Also, materials that are not compressible enough to be manufactured as traditional tablets often can be made into minitabs, says Farrenkopf.

The challenges of multiparticulates

Multiparticulates have disadvantages as well. Process development for multiparticulates is more complex than for standard tablets. Additional steps such as particle coating, extrusion, and sizing add to process complexity. For the same reason, multiparticulates also are more difficult and more expensive to manufacture than standard tablets. Some aspects of manufacturing minitabs such as flowing powders into the small dies represent a technological challenge.

It makes sense to choose a multiparticulate approach for applications such as pediatric drugs, multidrug dosage forms, and dosage forms that combine an initial burst with controlled release, says Farrenkopf. Otherwise, multiparticulates' complexity likely would prompt manufacturers to consider simpler dosage forms such as standard monolithic matrix tablets or bilayer tablets, as long as they can accomplish the same objective.


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