Somatostatin containing biodegradable microspheres prepared by a modified solvent evaporation method based on W/O/W-multiple emulsions

Biodegradable polyester microspheres containing somatostatin acetate, a peptide drug, were prepared by a modified solvent evaporation method based on the formation of multiple W/O/W-emulsions. The resulting microspheres were characterized with respect to drug loading, encapsulation efficiency and morphological characteristics. Various methods for extracting the peptide from the microspheres were compared. Of all parameters investigated, factors affecting the properties of the primary W/O-emulsion, such as the phase volume ratio and total volume, were of major importance. A small volume of internal aqueous phase and an intermediate volume of organic solvent were favorable to achieve high drug encapsulation efficiencies. Replacing methylene chloride as an organic solvent with ethyl acetate reduced the encapsulation efficiency and resulted in more porous microspheres. Except for microspheres prepared with very low molecular weight polymers, the encapsulation efficiency was not affected by the polymer type (poly(L-lactide), poly(D,L-lactide), poly (D,L-lactide/glycolide)) and molecular weight. The preparation conditions substantially affected the morphology and porosity of the microspheres.