IN-VITRO AND IN-VIVO EVALUATION OF MUCOADHESIVE MICROSPHERES PREPAREDFOR THE GASTROINTESTINAL-TRACT USING POLYGLYCEROL ESTERS OF FATTY-ACIDS AND A POLY(ACRYLIC ACID) DERIVATIVE

Two types of polyglycerol ester of fatty acid (PGEF)-based microsphere s were prepared: Carbopol 934P (CP)-coated microspheres (CPC-microsphe res) and CP-dispersion microspheres (CPD-microspheres). Comparative st udies on mucoadhesion were done with these microspheres and PGEF-based microspheres without CP (PGEF-microspheres). In an in vitro adhesion test, the CPD-microspheres adhered strongly to mucosa prepared from ra t stomach and small intestine because each CP particle in the CPD-micr osphere was hydrated and swelled with part of it remaining within the microsphere and part extending to the surface serving to anchor the mi crosphere to the mucus layer. The gastrointestinal transit patterns af ter administration of the CPD-microspheres and PGEF-microspheres to fa sted rats were fitted to a model in which the microspheres are emptied from the stomach monoexponentially with a lag time and then transit t hrough the small intestine at zero-order. Parameters obtained by curve fitting confirmed that the gastrointestinal transit time of the CPD-m icrospheres was prolonged compared with that of the PGEF-microspheres. MRT in the gastrointestinal tract was also prolonged after administra tion of the CPD-microspheres compared with that following the administ ration of the PGEF-microspheres.