Effect of process variables on the microstructure of hollow hydroxyapatite microspheres prepared by a glass conversion process

Solid microspheres (diameter = 106–150 μm) of a Li2O–CaO–B2O3 glass were reacted in a K2HPO4 solution to form hollow hydroxyapatite (HA) microspheres. The effect of the temperature (25°–60°C), K2HPO4 concentration (0.01–0.25M), and pH (9–12) of the solution on the diameter (d) of the hollow core normalized to the diameter (D) of the HA microspheres, the surface area, and the pore size of the microsphere wall was studied. The statistically significant process variables that influenced these microstructural characteristics were evaluated using a factorial design approach. While the pH had little effect, the concentration of the solution had a marked effect on d/D, surface area, and pore size, whereas temperature markedly influenced d/D and pore size, but not the surface area. The largest hollow core size (d/D value ≈ 0.6) was obtained at the lowest temperature (25°C) or the lowest K2HPO4 concentration (0.02M), while microspheres with the highest surface area (140 m2/g), with pores of size 10–12 nm were obtained at the highest concentration (0.25M). The consequences of these results for potential application of these hollow HA microspheres as devices for local delivery of proteins, such as drugs or growth factors, are discussed. I