Film coating of pellets with insoluble polymers obtained in situ crosslinking in the fluidized bed

Abstract

Abstract A novel technique for the manufacture of water-insoluble film coatings on drug-loaded saccharose pellets is described. The method is based on the simultaneous spraying of aqueous solutions of a film-forming polymer and an appropriate crosslinking agent. Crosslinking of the polymer was achieved in situ in the film during coating of the pellets in a fluidized bed. Uniform film coatings were formed without additives. Pan coating with sequential spraying of the components yielded similar results, however, it was more time consuming. The anionic polymer, sodium alginate, was combined with different cationic crosslinking agents, such as calcium ions, aluminum ions, Cetrimide (tetradecyltrimethylammonium bromide), and Eudragit E (copolymer of dimethylaminoethylmethacrylate and neutral methacrylic acid esters) (in 0.1 N HCl) in aqueous solutions. The swelling behavior of the cast films in water depended on the crosslinking component and the film thickness. For studying the in vitro drug release through the film coatings, the pellets were drug-loaded with acetaminophen and indomethacin as model drugs. Alginate films crosslinked with calcium ions showed the most promising features for controlled drug release. The release rate of the model drug acetaminophen proved to be almost independent of the pH of the dissolution fluid (pH 7.4 phosphate buffer, 0.1 N HCl). During drug release, the coatings did not disintegrate in 0.1 N HCl, but slowly disintegrated in buffer solution. Indomethacin was released at considerably smaller rates.