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 mu m. 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 (R). The Aerolizer (R) 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 p,m. The deposition pattern of the originator powder delivered with the Exubera (R) device showed significantly lower fine particle fractions and higher residues in comparison to the Aerolizer (R) 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 (R) product. With an optimised powder having an increased particle fraction smaller than 2 mu m more insulin may reach the deeper lung. Therefore, a lower dose could be used for an effective diabetic therapy. (C) 2009 Elsevier B.V. All rights reserved.