Abstract
The water-in-oil solvent evaporation method with premix membrane homogenization was investigated to improve productivity of the preparation of narrowly size-distributed poly(lactide-co-glycolide) (PLGA) microspheres for rifampicin lung delivery as dry aerosols. Using ethyl acetate as organic solvent, a coarse oil-in-water emulsion (or premix) was prepared under magnetic stirring and homogenized by extrusion through a Shirasu porous glass (SPG) membrane (5.9 μm porosity). Microspheres were obtained after dilution and solvent evaporation. Formulation parameters investigated were: PLGA concentration, transmembrane pressure and oil:water volume ratio. The optimal formulation parameters were then applied to prepare rifampicin-loaded microspheres. Loaded microspheres were 1.72 ± 0.16 μm in diameter with a span of 0.86 ± 0.04 and a rifampicin content of 52 ± 6 μg/mg microspheres. Release studies in phosphate-buffered saline showed a linear release profile with 40% rifampicin release over 4.5 days. The MMAD of 2.63 μm of freeze-dried microspheres should be suitable for aerosol administration and delivery into the rat lungs by intratracheal insufflation.
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