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 mic rospheres were characterized with respect to drug loading, encapsulati on efficiency and morphological characteristics. Various methods for e xtracting the peptide from the microspheres were compared. Of all para meters 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 inte rmediate volume of organic solvent were favorable to achieve high drug encapsulation efficiencies. Replacing methylene chloride as an organi c 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-lacti de), poly (D,L-lactide/glycolide)) and molecular weight. The preparati on conditions substantially affected the morphology and porosity of th e microspheres.