Cushion-coated Pellets for Tableting Without External Excipients.

Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may negatively affect the release control mechanism of pellets, and subunits may not be readily available after intake. Application of a cushioning layer to the starting units is here proposed as a strategy to obtain tablets with satisfactory mechanical strength, rapid disintegration and maintenance of the expected release profile of individual subunits while avoiding the use of mixtures of pellets and excipients to promote compaction and limit the impact of the forces involved. Cushion-coating with PEG1500, a soft and soluble material, was proved feasible provided that the processing temperature was adequately controlled. Cushioned gastro-resistant pellets were shown to consolidate under relatively low compaction pressures, which preserved their inherent release performance after tablet disintegration. Adhesion problems associated with the use of PEG1500 were overcome by applying an outer Kollicoat® IR film. Through design of experiment (DoE), robustness of the proposed approach was demonstrated, and the formulation as well as tableting conditions were optimized. The tableted cushion-coated pellet systems manufactured would allow a relatively high load of modified-release units to be conveyed, thus setting out a versatile and scalable approach to oral administration of multiple-unit dosage forms.