Gastro-resistant multiparticulate dosage form for mesalazine colon delivery in paediatric patients

The aim of this work was to develop and characterize gastro-resistant multiparticulate systems for mesalazine colon delivery to be easily dispersed in water and swallowed by children. Mesalazine microparticles, containing stearic acid, carnauba wax and Eudragit L, were obtained by spray-congealing. "Excipient microparticles" of mannitol/lecithin were prepared by spray-drying. Mesalazine lipid microparticles, non-agglomerating per se, were agglorerated by blending in turbula with mannitol/lecithin spray-dried microparticles in different ratio (2:1, 4:1, 6:1 and 8:1). The lipidic microparticles agglomerates were characterized by Optical Microscopy, Scanning Electron Microscopy, Differential Scanning Calorimetry and X-ray Powder Diffraction. Gastro-resistance and mesalazine release were evaluated by dissolution tests (USP XXXI Apparatus) at variable pH (2h in HCl 0.1 N and 6h in phosphate buffer pH 7.4). The lipidic microparticles showed smooth, glossy and sticky surface, and rounded shape. the agglomerates presented a less polish surface, but always a rounded shape. During the tumbling process, the lecithin's compatibility with the wax material of lipid microparticles favours the deposition of "excipient microparticles" all over the surface. As the ratio of the "excipient microparticles" increased, the area related to the melting of mannitol was increased. This effect was confirmed from the X-ray Powder Diffraction analysis. The dissolution profile showed a drug modified release: in acid medium the formulations were gastroresistant with less of 10% drug release (except for the agglomerates 2:1 where the higher amount of lechitin in the "excipient microparticles" acts as a surfactant), while in phosphate buffer the mesalazine was released in 4-5 hours. Lipidic microparticles preparated by spray congealing are gastroresistant; their wettability can be incresed be increased by their agglomaration with mannitol/lecithin microparticles