Purpose: The aim of this work was to develop and characterize gastro-resistant multiparticulate systems for mesalazine colon delivery capable to facilitate the dispersion in water and the intake by children. Methods: 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 agglomerated 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 and agglomerates were characterized by optical microscopy, Scanning Electron Microscopy, Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (PDXR). Gastro-resistance and drug release were evaluated by dissolution tests at variable pH (2h in HCl 0.1N 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 lipid microparticles favours the deposition of “excipient microparticles” all over the surface. As the ratio of “excipient microparticles” increases the thickness of coating raises. The DSC and PDXR analyses strengthened this hypothesis. During the dissolution test less than 10% of loaded mesalazine was released in acidic medium (except for agglomerates 2:1 where the release was about 15%), while in phosphate buffer the drug was released in 4-5 hours. The presence of excipient microparticles reduced the tendency to floatation of lipid microparticles improving their wettability. Conclusion: Lipidic microparticles prepared by spray congealing are gastroresistant; their wettability can be increased by agglomeration with mannitol/lecithin microparticles. The agglomeration technology can make feasible the delivery of gastro-resistant system for extemporaneous oral use in small children.
Gastro-resistant multiparticles for mesalazine colonic delivery in pediatric patients / A.G. Balducci; P. Colombo; C. Cavallari; L. Rodriguez; F. Sonvico; A. Rossi. - STAMPA. - (2009), pp. 24-24. (Intervento presentato al convegno 3rd A.It.U.N. Annual Meeting tenutosi a Salerno (SA) Italy nel March 6-7, 2009).
Gastro-resistant multiparticles for mesalazine colonic delivery in pediatric patients.
CAVALLARI, CRISTINA;RODRIGUEZ, LORENZO;
2009
Abstract
Purpose: The aim of this work was to develop and characterize gastro-resistant multiparticulate systems for mesalazine colon delivery capable to facilitate the dispersion in water and the intake by children. Methods: 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 agglomerated 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 and agglomerates were characterized by optical microscopy, Scanning Electron Microscopy, Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (PDXR). Gastro-resistance and drug release were evaluated by dissolution tests at variable pH (2h in HCl 0.1N 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 lipid microparticles favours the deposition of “excipient microparticles” all over the surface. As the ratio of “excipient microparticles” increases the thickness of coating raises. The DSC and PDXR analyses strengthened this hypothesis. During the dissolution test less than 10% of loaded mesalazine was released in acidic medium (except for agglomerates 2:1 where the release was about 15%), while in phosphate buffer the drug was released in 4-5 hours. The presence of excipient microparticles reduced the tendency to floatation of lipid microparticles improving their wettability. Conclusion: Lipidic microparticles prepared by spray congealing are gastroresistant; their wettability can be increased by agglomeration with mannitol/lecithin microparticles. The agglomeration technology can make feasible the delivery of gastro-resistant system for extemporaneous oral use in small children.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
