1 Department of Pharmacy, Faculty of Pharmaceutical Sciences, Københavns Universitet2 Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet3 University College London4 Novozymes Biopharma A/S5 Novo Nordisk A/S6 Pharmaceutical Technology and Engineering, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet7 Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet8 University College London9 Pharmaceutical Technology and Engineering, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet
PURPOSE: It is imperative to understand the particle formation mechanisms when designing advanced nano/microparticulate drug delivery systems. We investigated how the solvent power and volatility influence the texture and surface chemistry of celecoxib-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles prepared by spray-drying. METHODS: Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA). RESULTS: Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. CONCLUSIONS: The particle formation process is mainly governed by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition.
Pharmaceutical Research, 2013, Vol 30, Issue 4, p. 1065-1076