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Multiparticulates: A Flexible Approach for New Dosage Forms

Multiparticulate (MP) technology is a well-established and versatile tool for solving a wide range of drug delivery problem statements, including oral modified and controlled release, developing patient-centric dosage forms, and achieving flexibility in dose and dosage form presentation. MP technology can also be combined with other formulation technologies, such as amorphous forms or permeation enhancement to improve bioavailability in certain cases. With such diversity in potential applications, it is natural to ask when multi-particulates are the ideal choice, and how formulations are selected.

Technology selection to evaluate a multi-particulate approach starts with defining the target product profile (TPP) for a compound. The TPP may encompass technical drivers such as the need to address low bioavailability, pharmacokinetic considerations such as requirements for extended release, or the need for localised delivery in the gastrointestinal tract. External product drivers can also be an important part of the TPP, including product lifecycle management, tailoring dosage forms for specific patient populations, and dose flexibility requirements.

In the earlier stages of clinical development, a range of dose sizes may be required for dose-finding studies, and making a range of different tablets with varying dose strengths can add to the complexity of the development process. A single, flexible intermediate such as a multi-particulate would be beneficial if it could be easily pivoted from one presentation to another.

There is a growing market, too, for age-appropriate formulations, particularly for paediatric populations who are unable to swallow a traditional tablet or capsule. For some alternative presentations, taste masking may be essential. In all of these cases, the answer may lie in a multi-particulate design.

Multiparticulates are small, discrete units of the formulated drug, each with a uniform fractional dose. Any required functionality is already built-in to each discrete unit. These individual units might be microspheres, pellets, granules, or even mini tablets, with sizes falling into the 100µm to the millimetre size range. It is easy to scale the dose by varying the quantity of the discrete formulated multi-particulates into a particular dosage form, such as a capsule or sachet. In particular, when a modified or controlled release profile is required, this approach can be faster and less costly and time-consuming to create dosage forms in multiple different strengths.

Multiparticulate Advantages

A key advantage of multi-particulates is their ability to offer an extremely wide range of release characteristics, which is dictated by the particles’ formulation, size and functional coatings, as shown in Figure 1. Options include immediate-release or controlled-release lipid multi-particulates, coatings to provide taste masking, controlled-release or pH-dependent properties, or fixed-dose combinations by blending multi-particulates made from different compounds together.

Coatings applied to the multi-particulates can confer a variety of benefits. They can be used for taste masking, which is particularly important for sprinkled dosing in paediatric populations. They are also used to protect drugs in the acid environment of the stomach and to enable their release further down the gastrointestinal tract, such as in the jejunum or colon.