In vitro degradation study of polyester microspheres by a new HPLC method for monomer release determination

Biodegradable polyesters have increasing importance as materials used for t he preparation of microspheres. The knowledge of their degradation process is important to prepare microparticulate delivery systems with suitable dru g release rates. In this work an in vitro degradation study of empty and dr ug loaded microspheres is described. Three different polyesters were used: two poly-D,L-lactides of different molecular weight and a poly-D,L-lactide- co-glycolide (50:50). Diazepam has been chosen as the model drug. Solvent e vaporation and spray-drying were used as preparation methods. To study the polymer degradation process, a new HPLC method is proposed for the direct a nd (in the case of the copolymer) simultaneous determination of the monomer (s): lactic acid (LA) and glycolic acid (GA). SEM and particle size analysi s highlight the different characteristics of the particles, depending on th eir preparation method: spray-dried spheres result to be always smaller wit h respect to particles obtained by solvent evaporation. The results obtaine d indicate in particular that: the preparation methods play an important ro le in determining the degradation behaviour of microspheres, as unloaded sp ray-dried particles are characterized by a higher monomer release fate with respect to microspheres obtained by solvent evaporation; PLGA spheres degr ade faster than PDLLA microparticles, according to the higher hydrophilicit y of the copolymer; the two monomers are released at a different rate in th e case of PLGA (faster for GA, slower for LA); the presence of diazepam inc reases the polymer degradation rate, with respect to empty particles. (C) 1 998 Elsevier Science BN. All rights reserved.