Preparation and in vitro characterisation of mucoadhesive polymeric microspheres as intra-nasal delivery systems

Microspheres of hydrophilic polymers were prepared by the w/o emulsification solvent evaporation technique with a potential application as drug carriers for nasal administration by insufflation. The microspheres had a median particle size of 38 +/- 1.7 mu m (Carbopol 934P), 38.6 +/- 1.8 mu m (Chitosan), 33.6 +/- 7.2 mu m (HPMC), and 16.5 +/- 4.3 mu m (PVA) prepared using a stirring speed of 2000 rpm for 4 or 4.5 h at 80 degrees C. Chitosan and PVA microspheres were spherical and smooth-surfaced while Carbopol 934P and HPMC were of irregular shape with a rough surface morphology. For Carbopol 934P, the microsphere size was inversely proportional to stirring speed (1200-2000 rpm), and to the percentage of the emulsifier (Arlacel A, 0.2-1% w/w) and proportional to the percentage of core materials (0.2-0.5% w/w). FITC-dextran (Mw 4300 Dal was incorporated into the microspheres with an efficiency of 81 +/- 3.6% (Carbopol 934P), 55 +/- 20% (PVA), 44 +/- 6.7% (HPMC), and 36 +/- 2.7% (Chitosan). The change in initial concentration of FITC, dextran (0-15% w/w) had no effect on the particle size of Carbopol 934P microspheres. The rank order of mucoadhesion for the polymeric microspheres was Carbopol 934P > Chitosan = PVA = HPMC, although Chitosan was > HPMC. The change in content of FITC-dextran showed no significant effect on the mucoadhesive strength of Carbopol 934P microspheres within the concentration range of 0-12% w/w. The FITC-dextran was released from the microspheres initially at a constant rate. However the release rate subsequently decreased over the 24 h test period. No differences were observed for release from Carbopol 934P, PVA and HPMC: all exhibited faster release than that achieved from the Chitosan microspheres which exhibited a size-dependent release effect. (C) 1997 Elsevier Science B.V.