The effect of particle microstructure on the somatostatin release from poly(lactide) microspheres prepared by a W/O/W solvent evaporation method

Abstract

Somatostatin acetate-containing poly(lactide) microspheres were prepared by a W/O/W multiple emulsion solvent evaporation method. The resulting microspheres were characterized with respect to encapsulation efficiency, drug release and morphological properties (scanning electron microscopy). The addition of various buffers (pH 2.2, 3.0, 4.0 or 5.0) or salts (NaCl or CaCl 2) to the internal aqueous and/or external aqueous phase affected the osmotic pressure gradient between the two aqueous phases and the solvent/ water flux during the microsphere formation. Addition to the internal aqueous phase promoted the influx of water from the external aqueous phase. This resulted in more porous microspheres. Reversing the osmotic pressure gradient by adding salts to the external aqueous medium resulted in the formation of a dense and homogeneous polymer matrix. Intermediate structures were obtained through variations in the salt concentration gradient. The drug release profiles consisted of a rapid drug release phase followed by a slow release phase. The initial peptide release from the microspheres could be controlled through changes in the microstructure of the microspheres, with the peptide being released faster from the more porous microspheres. Lower encapsulation efficiencies were obtained with the more porous microspheres.