Purpose. Mesalazine is an antinflammatory drug used for ulcerative colites and Crohn’s disease. In pediatrics there is the need to improve the patient compliance avoiding dosage forms that difficult swallowed by young people. The aim of this work was the preparation and characterisation of soft agglomerates of mesalazine multiparticulate systems for colon delivery capable to facilitate the dispersion in water and the intake by children. Methods. Two formulations of mesalazine microparticles, both containing stearic acid and carnauba wax and differing only for the presence of 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 agglomerated by blending in turbula with mannitolo/lecithin spray-dried microparticles in different ratio (2:1, 4:1, 6:1, 8:1). The agglomerates were characterized by optical microscopy, Scanning Electron Microscopy and X-ray Powder Diffraction. Gastro-resistance and drug release were evaluated by dissolution test at variable pH (HCl 0.1N for 2h and 6h in phosphate buffer pH 7.4). Samples were collected at fixed times and analyzed by UV spectroscopy (λ 301 nm and 330 nm in acidic and alkaline medium, respectively). Results. The surface of lipidic microparticles was smooth and sticky, while the agglomerate morphology appeared rounded. During the tumbling process, the lecithin’s compatibility with the wax material of lipidic microparticles favours the deposition of “excipient microparticles” on the surface. As the ratio of “excipient microparticle” increases the thickness of coating raises. In particular, in the 2:1 ratio more layers of excipient microparticles are deposited on the lipidic microparticles. The dissolution profile showed a drug modified release: in acid medium the formulations are gastroresistant with less of 10% drug release, while in phosphate buffer the mesalazine is released in 4-5 hours. The presence of excipient microparticles reduced the tendency to floatation of lipid microparticles improving their wettability. Conclusion. The agglomeration technology can allow the manufacturing of gastroresistant dosage form suitable for extemporaneous oral use in children. Lipidic microparticles prepared by spray congealing are gastroresistant; their wettability can be increased by agglomeration with mannitol/lecithin microparticles.

BALDUCCI A.G, COLOMBO P, CAVALLARI C, RODRIGUEZ L, SONVICO F, COLOMBO G, et al. (2008). Soft agglomerates of mesalazine multiparticles for colonic delivery in pediatric patients.. ATLANTA : s.n.

Soft agglomerates of mesalazine multiparticles for colonic delivery in pediatric patients.

CAVALLARI, CRISTINA;RODRIGUEZ, LORENZO;
2008

Abstract

Purpose. Mesalazine is an antinflammatory drug used for ulcerative colites and Crohn’s disease. In pediatrics there is the need to improve the patient compliance avoiding dosage forms that difficult swallowed by young people. The aim of this work was the preparation and characterisation of soft agglomerates of mesalazine multiparticulate systems for colon delivery capable to facilitate the dispersion in water and the intake by children. Methods. Two formulations of mesalazine microparticles, both containing stearic acid and carnauba wax and differing only for the presence of 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 agglomerated by blending in turbula with mannitolo/lecithin spray-dried microparticles in different ratio (2:1, 4:1, 6:1, 8:1). The agglomerates were characterized by optical microscopy, Scanning Electron Microscopy and X-ray Powder Diffraction. Gastro-resistance and drug release were evaluated by dissolution test at variable pH (HCl 0.1N for 2h and 6h in phosphate buffer pH 7.4). Samples were collected at fixed times and analyzed by UV spectroscopy (λ 301 nm and 330 nm in acidic and alkaline medium, respectively). Results. The surface of lipidic microparticles was smooth and sticky, while the agglomerate morphology appeared rounded. During the tumbling process, the lecithin’s compatibility with the wax material of lipidic microparticles favours the deposition of “excipient microparticles” on the surface. As the ratio of “excipient microparticle” increases the thickness of coating raises. In particular, in the 2:1 ratio more layers of excipient microparticles are deposited on the lipidic microparticles. The dissolution profile showed a drug modified release: in acid medium the formulations are gastroresistant with less of 10% drug release, while in phosphate buffer the mesalazine is released in 4-5 hours. The presence of excipient microparticles reduced the tendency to floatation of lipid microparticles improving their wettability. Conclusion. The agglomeration technology can allow the manufacturing of gastroresistant dosage form suitable for extemporaneous oral use in children. Lipidic microparticles prepared by spray congealing are gastroresistant; their wettability can be increased by agglomeration with mannitol/lecithin microparticles.
2008
2008 AAPS Annual Meeting
1213
1213
BALDUCCI A.G, COLOMBO P, CAVALLARI C, RODRIGUEZ L, SONVICO F, COLOMBO G, et al. (2008). Soft agglomerates of mesalazine multiparticles for colonic delivery in pediatric patients.. ATLANTA : s.n.
BALDUCCI A.G; COLOMBO P; CAVALLARI C; RODRIGUEZ L; SONVICO F; COLOMBO G; ROSSI A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/67990
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