Multi-particulates or pellets are an important CR formulation strategy, with the advantage of supporting a wide range of dose strengths by delivering simply different pellet quantities, for adult and paediatric populations.
This is generally not possible for monolithic dosage forms, like hydrophilic matrices, since their weight multiples result in differently sized dosage forms, which, in turn, affects drug release (due to mechanistic differences from pellets). There are a number of established processes for CR pellet preparation, most of which require barrier coatings to attain CR functionality.
Pellet formulations are generally associated with less in vivo variability than their monolithic counterparts, since they consist of a large number of release-controlling units. This is largely due to their different interplay with the GI tract, especially their spatial distribution. There are, however, unique challenges associated with CR pellets, mainly due to more complex processing, higher production costs and release barrier design criteria.
Palletization and multi-particulate core preparation can generally be categorized as follows:
- Matrix architecture
- Layered architecture
Cores with matrix architecture are characterized by API being distributed uniformly throughout the cores, which are generally formed by converting powders or granules into spherical or near-spherical particles with diameters of typically 0.5 to 1.5 mm and shapes that lend themselves to coating.
Cores with layered architecture are prepared by depositing particulates onto seed particles, either via a liquid carrier or as dry powders, and converting them into API-containing solid layers.
Processes of palletization and multi-particulate core preparation
- Extrusion – spheronisation (e–S)
- Direct palletization (via rotary granulation)
- Dry powder layering
- Spray layering
- Hot-melt palletization
- Mini-tablets/Mini-matrices
