Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods

Somatostatin, a therapeutic peptide drug, was entrapped within polymeric microspheres made from high molecular weight poly (D,L-lactide/glycolide) (PLGA) or low molecular weight poly (D,L-lactide) (PLA) by various modifications of the O/W-solvent evaporation method. The drug was either dispersed as solid (dispersion method), dissolved with the aid of a co-solvent (co-solvent method) or emulsified as an aqueous solution (W/O/W-multiple emulsion method) in the organic polymer solution prior to emulsification into an external aqueous phase. Additionally, a non-aqueous O/O-method was evaluated for the formation of the microspheres. Acceptable encapsulation efficiencies were obtained with all methods, regardless of the physical state of drug and the polymer type. The total volume of organic solvent and the co-solvent content were found to be important preparation factors of the O/W-co-solvent method. A more lipophilic solvent system appeared to favor efficient drug encapsulation. Replacing the widely used but toxic methylene chloride with ethyl acetate resulted in significantly lower drug loadings. The preparation method substantially affected the morphology of the microspheres and the drug release. (C) 1998 Elsevier Science B.V.