Preparation and Evaluation of Methotrexate-Loaded Biodegradable Polyanhydride Microspheres

Methotrexate-loaded biodegradable polyanhydride microspheres were prepared by modified hot-melt technique and aqueous solvent evaporation technique. The effect of particle size, drug loading and microencapsulation technique on the in vitro drug release was studied. The in vitro release of methotrexate was evaluated using an automated flow-through cell system. The release profile consisted of burst release and sustained release phases. The burst release from the microspheres prepared by the modified technique was lower than that from the aqueous solvent evaporation technique. In addition, the microspheres with lower loadings released smaller amounts during the burst release phase. For a given loading and processing technique, the amount released by burst decreased with an increase in particle size. The microspheres prepared by the modified hot-melt technique with 10% loading and 177-250 μm size fraction 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 implantation at 48 hours post-implantation.