Insulin-micro- and nanoparticles for pulmonary delivery

The pulmonary application of insulin via oral inhalation turned out to be a promising option due to the large surface area and good vascularisation the lung is offering for the systemic delivery of peptides and proteins. To have a systemic effect, inhaled particles need to attain the alveoli and should therefore have a mass median diameter of less than 2 μm. To achieve such a particle size for dry powders spray drying of drug solutions is a common method. In this study, a nano-precipitation of the drug prior to spray drying was carried out using the solvent change method. The produced powders were compared to powder produced out of a solution and to the marketed product Exubera ®. The Aerolizer ® device was used representing a simple capsule-based dry powder inhaler. It could be shown that the insulin yield of the precipitation process highly depends on the used pH-value and the amount of non-solvent. Also the particle size after spray drying decreases with increasing amount of non-solvent. Aerodynamic assessment of insulin powders showed that the precipitated insulin particles behave superior to powders spray dried from solution with respect to particles smaller than 2 μm. The deposition pattern of the originator powder delivered with the Exubera ® device showed significantly lower fine particle fractions and higher residues in comparison to the Aerolizer ® device. In summary, precipitated insulin particles combined with the delivery from a standard capsule-based inhaler were found to be at least as effective in vitro as the marketed Exubera ® product. With an optimised powder having an increased particle fraction smaller than 2 μm more insulin may reach the deeper lung. Therefore, a lower dose could be used for an effective diabetic therapy.