THE EFFECT OF PARTICLE MICROSTRUCTURE ON THE SOMATOSTATIN RELEASE FROM POLY(LACTIDE) MICROSPHERES PREPARED BY A W O/W SOLVENT EVAPORATION METHOD/

Somatostatin acetate-containing poly(lactide) microspheres were prepar ed by a W/O/W multiple emulsion solvent evaporation method. The result ing microspheres were characterized with respect to encapsulation effi ciency, drug release and morphological properties (scanning electron m icroscopy). The addition of various buffers (pH 2.2, 3.0, 4.0 or 5.0) or salts (NaCl or CaCl2) to the internal aqueous and/or external aqueo us phase affected the osmotic pressure gradient between the two aqueou s phases and the solvent/water flux during the microsphere formation. Addition to the internal aqueous phase promoted the influx of water fr om the external aqueous phase. This resulted in more porous microspher es. Reversing the osmotic pressure gradient by adding salts to the ext ernal aqueous medium resulted in the formation of a dense and homogene ous polymer matrix. Intermediate structures were obtained through vari ations in the salt concentration gradient. The drug release profiles c onsisted of a rapid drug release phase followed by a slow release phas e. The initial peptide release from the microspheres could be controll ed through changes in the microstructure of the microspheres, with the peptide being released faster from the more porous microspheres. Lowe r encapsulation efficiencies were obtained with the more porous micros pheres.