Effects of inner water volume on the peculiar surface morphology of microspheres fabricated by double emulsion technique

Poly(D,L-lactide-co-glycolide) (PLG, 65:35) was used to encapsulate bovine serum albumin (BSA) using a water-in-oil-in-water (W/O/W) double emulsion solvent extraction technique. To investigate the effects of an inner water/oil ratio on microsphere characteristics, microspheres were fabricated using four different formulations with a fixed oil volume of 12 ml and the inner aqueous phase volume of 0.2 ml, 0.3 ml, 0.4 ml or 0.5 ml, respectively. Spherical microspheres were obtained after collection by filtration for formulations employing any of the four different inner water/oil ratios. However, microspheres with smaller inner water volumes tend to collapse after vacuum drying. The surface of the formulation with a higher inner water/oil ratio was shown to possess many more pores than that of the formulations with lower inner water/oil ratios. These pores may facilitate the water withdrawal during vacuum drying. Furthermore, microspheres with the lowest inner water/oil ratio (1/60) had higher initial burst release due to its larger surface area. However, microspheres with the highest inner water volume yield a faster release profile of BSA due to interconnected voids within microspheres and more pores on the surface. Therefore, the inner water/oil ratio is a crucial factor in the W/O/W double emulsion technique affecting the morphology and release kinetics of the resulting microspheres.