Zinc-alginate microparticles for controlled pulmonary delivery of proteins prepared by spray-drying

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Katrin MöbusRoland Bodmeier

Abstract

The aim of this study was to prepare novel Zn(2+)-cross-linked alginate microparticles for controlled pulmonary delivery of protein drugs via a simple one-step spray-drying process and to physicochemically characterize these systems. Microparticles were prepared by spray-drying aqueous alginate solutions, containing the model protein BSA, Zn(NH(3))(4)SO(4), and optionally additional excipients. Upon ammonia evaporation, the alginate was cross-linked by Zn(2+)-ions. The microparticles were characterized by SEM, laser and X-ray diffraction, gel electrophoresis, aerodynamic particle size, and drug release measurements. Particles in a size range suitable for deep lung administration were obtained. Pure alginate microparticles were spherical in shape, whereas the addition of zinc led to a more collapsed geometry. Protein release depended on the (i) alginate:ZnSO(4) ratio (minimum release rate at 2:1); (ii) BSA content (decreasing release rate and extent with decreasing BSA content); (iii) type of release medium (increasing release rate with increasing phosphate concentration). The emitted microparticle dose was high for all formulations (∼90%). Fine particle fractions (FPF, depositing in the deep lung) up to 40% could be achieved. T...Continue Reading

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