Two Contrasting Failure Modes of Enteric Coated Beads.

This study aimed to elucidate the mechanisms and kinetics of coating failure for enteric coated beads exposed to high-humidity conditions at different storage temperatures. Enteric coated beads were placed on high-humidity conditions (75 to 98% relative humidity (RH)) in the temperature range of 5 to 40°C. These stability samples of beads were tested for acid dissolution and water activity and also analyzed with SEM, X-ray CT, and DMA. Exposure of enteric coated beads to high humidity led to increased gastric release of drug which eventually failed the dissolution specification. SEM showed visible cracks on the surface of beads exposed to 5°C/high humidity and fusion of enteric beads into agglomerates at 40°C/high humidity. In a non-destructive time elapse study, X-ray CT demonstrated swelling of microcrystalline cellulose cores, crack initiation, and propagation through the API layer within days under 5°C/98% RH storage conditions and ultimately fracture through the enteric coating. DMA data showed a marked reduction in T of the enteric coating materials after exposure to humidity. At 5°C/high humidity, the hygroscopic microcrystalline cellulose core absorbed moisture leading to core swelling and consequent fracture through the brittle API and enteric layers. At 40°C (high humidity) which is above the T of the enteric polymer, enteric coated beads coalesced into agglomerates due to melt flow of the enteric coating. We believe it is the first report on two distinct failure models of enteric coated dosage forms.