PREPARATION AND EVALUATION OF METHOTREXATE-LOADED BIODEGRADABLE POLYANHYDRIDE MICROSPHERES

Methotrexate-loaded biodegradable polyanhydride microspheres were prep ared by modified hot-melt technique and aqueous solvent evaporation te chnique. The effect of particle size, drug loading and microencapsulat ion technique on the in vitro drug release was studied. The in vitro r elease of methotrexate was evaluated using an automated flow-through c ell system. The release profile consisted of burst release and sustain ed release phases. The burst release from the microspheres prepared by the modified technique was lower than that from the aqueous solvent e vaporation technique. In addition, the microspheres with lower loading s released smaller amounts during the burst release phase. For a given loading and processing technique, the amount released by burst decrea sed with an increase in particle size. The microspheres prepared by th e modified hot-melt technique with 10% loading and 177-250 mu m size f raction gave desirable prolonged release. This formulation was tested in vivo in rats by subcutaneous implantation. The peak serum level of methotrexate was reached between 15-18 hours compared to that between 0-3 hours observed following the administration of an equivalent dose of methotrexate solution. No microspheres were found at the site of im plantation at 48 hours post-implantation.