PREPARATION AND CHARACTERIZATION OF POLY(D,L-LACTIC-CO-GLYCOLIC ACID)MICROSPHERES CONTAINING DESFERRIOXAMINE

The iron chelator desferrioxamine (DFO) demonstrates antimalarial acti vity upon multiple or continuous parenteral administration. The aim of this study was to develop a controlled release system for the water-s oluble drug DFO based on poly (D,L-lactic-co-glycolic acid) (PLGA). PL GA microspheres containing DFO were prepared using the water-in-oil-in -water (w/o/w) solvent evaporation technique. The influence of formula tion parameters (internal phase volume and polymer concentration) on t he microsphere characteristics (particle size, porosity, encapsulation efficiency of DFO and DFO release profile were investigated. An incre asing internal phase volume at a fixed polymer concentration resulted in an increasing volume weight mean diameter, an increasing porosity a nd a decreasing encapsulation efficiency. An increasing PLGA concentra tion at a fixed internal phase volume resulted in a decreasing porosit y of the particles with an increased volume weight mean diameter and e ncapsulation efficiency of DFO. DFO was released from the microspheres in an initial burst (controlled by formulation parameters) followed b y marginal release and a pulse release at the time the microspheres st art to dissolve (20-30 days). The release of DFO was incomplete after complete dissolution of the microspheres. This is probably caused by t he instability of DFO at low pH, generated upon degradation of the PLG A matrix. (C) 1997 Elsevier Science B.V.