Development and characterization of high dosed layered pellets with polyvinyl based film coats for modified release applications

Pellets are small spherical oral solid dosage forms, which enjoy an increasing interest in pharmaceutical industry. A stable fluid bed manufacturing process for high drug containing pellets was developed. The pellets were coated with a novel film blend from Kollicoat® SR and Kollicoat® IR, resulting in a sustained drug release. The impact of the film coat composition and the pellet structure on the drug release was studied. Further studies were focused on the drug release mechanism from coated pellets. Therefore, the water influx into the pellets as well as the solubilization of drug inside the pellets was investigated non-invasively, using ESR and NMR technology. Additionally, the changes on the pellet surface during dissolution were monitored, using AFM. Finally, a possible release mechanism was postulated for high dosed pellets, coated with Kollicoat® SR and IR. The release mechanism concluded a water influx with a fast drug solubilization inside the pellets. Simultaneously, soluble film coat components were dissolved from the surface, leading to a porous film coat. An osmotic driven drug release mechanism was postulated, strongly dependent on the drug content of the pellets as well as their size.