ABSTRACT:
The present work was aimed to develop a pH sensitive mucoadhesive microspheres sustained drug delivery system of fluvastatin sodium, a water soluble and poorly bioavailable drug (24%), unstable at gastric pH. Mucoadhesive microspheres were formulated using polymethacrylate polymer (EL 100 and ES 100) having excellent mucoadhesive property. Microspheres formed were discrete, free flowing and exhibited good mucoadhesive properties. pH sensitive mucoadhesive microspheres were formulated by w/o/o double emulsion solvent diffusion method. Parameters such as particle size analysis, drug entrapment efficiency, scanning electron microscopy (SEM) analysis, in vitro wash-off test, in vitro release studies and drug polymer compatibility studies were investigated. Results showed that the polymer concentration affected size, entrapment efficiency, mucoadhesion property and drug release from the microspheres. The good result was obtained for the formulation F10 (Drug: EL 100 (1:2.5). At this ratio, the mean particle size, entrapment efficiency, swelling index of mucoadhesive microspheres was increased and drug release was sustained when compared to the other formulations. Also this formulation showed highest mucoadhesion time when compared to other formulations. This was confirmed in vitro wash-off test. Fourier Transform-Infra Red Spectroscopy (FT-IR) and Differential Scanning Calorimetric studies (DSC) did not show any drug, polymer interactions. The results of powder X-ray diffraction (PXRD) studies showed the reduced crystal nature of the drug. Conclusively, a pH sensitive mucoadhesive drug delivery system was successfully developed that showed sustained and delayed release up to 12 hours and could be potentially useful to overcome poor bioavailability problems associated with fluvastatin sodium.