Bead compacts. II. Evaluation of rapidly disintegrating nonsegregating compressed bead formulations

In this study, three techniques for the prevention or mitigation of polymer coat fracture on compaction of sustained-release beads into tablets were i nvestigated. All techniques in this paper were evaluated without the additi on of any cushioning excipients, but rather by spray coating these excipien ts to avoid segregation during product manufacturing. First it was shown th at use of swellable polymers such as polyethylene oxide (PEO) serves a uniq ue and effective role in preventing polymer coat rupture. PEO was spray coa ted between the ethylcellulose (EC) and microcrystalline cellulose (MCC) co ats to evaluate its cushioning effect The compacted PEO layered beads, on d issolution, disintegrated into individual beads with sustained drug release of up to 8 hr. It is postulated that the PEO was hydrated and formed a gel that acts as a sealant for the cracks formed in the ruptured polymer coati ng (sealant-effect compacts). Second; EC-coated drug-layered beads were als o over-coated with cushioning excipients such as polyethylene glycol (PEG) and MCC,vith an additional coating of a disintegrant. These beads were comp ressed at pressures of 125, 500, and 1000 pounds into caplets and, on disso lution testing, disintegrated into individual beads when the dissolution me dium was switched from simulated gastric to intestinal fluid. The dissoluti on profiles show that the polymer coat was partly disrupted on compaction, leading to a total drug release in 8-10 hr. Third, EC-coated beads were als o granulated with cushioning excipient and compressed. This approach also r esulted in a ruptured polymer coat on the beads, but at higher compaction p ressure produced a partially disintegrating matrix caplet that showed a nea rly zero-order sustained drug release for 24 hr. The effect of bead size an d polymer coat thickness was also investigated.