Porous Biodegradable Microspheres for Controlled Drug Delivery. I. Assessment of Processing Conditions and Solvent Removal Techniques

Abstract

Microspheres containing methylene blue and prednisolone acetate were prepared by one of three methods: freeze-drying, evaporation, and solvent-extraction-precipitation. An extremely porous structure was obtained by the freeze-dry and solvent-extraction-precipitation procedures. The specific surface area of 6.33-µm particles was 20.6 m²/g, or 35 times that of a particle devoid of pores, and the void space was 59–61%. The sphericity, size, and yields of the microspheres were influenced by the preparation procedure, surfactant type and concentration, temperature of the continuous phase, polymer concentration in the dispersed phase, and ratio of marker to polymer. The most suitable processing conditions were a polymer concentration of 5–10%, a marker loading of 10%, 0.1% sorbitan sesquioleate as the surfactant, and temperature adjustment of the continuous phase from 15 to 50°C following the addition of the dispersed phase. Complete release of the highly water soluble methylene blue occurred within 72 hr, while the less soluble prednisolone acetate released much more slowly, i.e., 90% after 7 days. The microspheres remained relatively intact during the in vitro release of methylene blue, confirming that the incorporated agent was confined to the walls of the porous network. Collapse of the polymer structure was evident after 7 days. The release therefore was believed to be governed principally by the solubility of the drug and the porosity of the matrix.