This paper describes a preparation method of D,L-lactic acid oligomer formulations capable of sustained release of proteins without any large initial burst in release. The oligomer formulations containing various proteins were prepared by a W/O emulsion method to examine the protein release. Briefly, the W/O emulsion of protein aqueous solution and oligomer/chloroform solution was prepared by probe sonication. Then, the powders obtained by freeze-drying the W/O emulsion were compression molded at 60-degrees-C into rods. As another method (mixing method), the protein was mixed with the oligomer at 45-60-degrees-C and the mixture was molded into rods similarly. Moreover, the resulting rods were ground into granules. The recovery of the oligomer formulation was about 95% and the formulation incorporated about 90% of the theoretical amount of proteins, irrespective of the type of proteins and oligomers used. Both the W/O and mixing methods permitted sustained release of proteins from the oligomer rods without any large initial burst when the protein loading was less than 20%. However, the release profile was different between the granules prepared by the two methods. For granules of sizes less than 200 mum prepared by the mixing method, greater than 50% of protein was released during the first day of the release test, irrespective of the oligomer molecular weight, the type of proteins, and their loading. On the contrary, the granules obtained by the emulsion method significantly reduced the extent of large initial burst in protein release. Light microscopic observations demonstrated a high homogeneity of protein dispersion through the oligomer formulation prepared by the W/O emulsion method, which led to the sustained release of proteins with a reduced initial burst. However, the emulsion method was associated with a loss in protein activity during preparation of the oligomer formulation. The emulsion method caused 45% and 63% loss in the biological activity of trypsin and insulin while about 10% of the activity was lost for the mixing method.
