Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method

This study describes the influence of preparation temperature on the various characteristics and release profiles of poly(DL-lactide-co-glycolide) (PLGA) microspheres. The bovine serum albumin (BSA)-loaded microspheres were prepared using the water-in-oil-in-water (w/o/w) technique with poly(vinyl alcohol) as surfactant in the external aqueous phase. We have varied the preparation temperature to observe its effect on microsphere characteristics such as the microsphere shrinking rate during formation, particle size, density, surface and internal morphology, BSA encapsulation efficiency, BSA initial release, microsphere degradation and BSA in vitro release behaviour. During fabrication, a low preparation temperature of 5 degreesC gives the fastest initial but the slowest overall shrinking rate. Microspheres formed at high temperatures of 38 degreesC and 42 degreesC on the other hand have the lowest initial yet the highest overall shrinking rate. Subsequently, microsphere mean size increases and the particle size distribution widens with increase in the preparation temperature. Although all the microspheres have a porous surface as well as internal structure, microspheres fabricated at high temperatures have a uniform internal pore distribution and a very thin dense skin layer, while microspheres fabricated at lower temperatures have a thicker but porous skin layer and bigger pores in the middle of the sphere. Microspheres formed at 33 degreesC are found to give the highest initial burst release. In terms of in vitro release, microspheres fabricated at low temperatures (5 degreesC, 15 degreesC and 22 degreesC) exhibit similar, steady rates. Microspheres formed at higher temperatures however give very low release rates after their initial release. The results obtained suggest that preparation temperature significantly affects microsphere formation, resulting in their structural and protein release profile differences. These differences ultimately work together to affect the initial release and overall release patterns of the microspheres. (C) 2000 Elsevier Science B.V. All rights reserved.