BEAD COMPACTS - I - EFFECT OF COMPRESSION ON MAINTENANCE OF POLYMER COAT INTEGRITY IN MULTILAYERED BEAD FORMULATIONS

Little information is available on the compactability of beads for ora l sustained release dosage forms. It is known that polymer-coated bead s may fuse together to produce a non-disintegrating controlled-release matrix tablet when compressed. This study evaluates the effect of com pression on beads with multiple layers of polymer and drug coat, and t he effect of cushioning excipients and compaction pressure on drug rel ease from compressed bead formulations. The multilayered beads consist of several alternating layers of acetaminophen (APAP) and polymer coa ts (Aquacoat(R)) with an outer layer of mannitol as a cushioning excip ient. Percent drug release versus time profiles showed that the releas e of drug decreases from noncompacted beads as the amount and number o f coatings increases, with only 43% of drug released in 24 hr for coat ed beads with 10 layers. It was shown that the compacted multilayered beads will disintegrate in gastrointestinal fluids, providing a useful drug release pattern. It was shown that beads of drug prepared by any method can be spray-layered with excipients such as Avicel and mannit ol. Spray-layering of the cushioning excipient onto beads can provide an effective way to circumvent segregation issues associated with mixi ng of the polymer-coated beads and powdered or spherical/nonspherical cushioning excipients. Spray layering of the cushioning excipient can also provide excellent flow properties of the final formulation as vis ually observed in our experiments. Triple-layered caplets (TLC) were a lso prepared with outer layers of Avicel PH-101 or polyethylene oxide (PEO), and a center layer of polymer-coated beads. For TLC, the polyme r coating on the beads fractured, and nondisintegrating matrix formula tions were obtained with both caplet formulations.