Pulmonary delivery of therapeutic peptides via dry powder inhalation: effects of micronisation and manufacturing

摘要: Pulmonary drug delivery is increasingly appreciated as a route of administration for systemically acting proteins and peptides. A respirable particle size the key requirement, but fragile nature many may be limitation application conventional production processes. The aim this study was to examine effect different micronisation processes on degradation aerodynamic properties GnRH-antagonist cetrorelix in order enable its by dry powder inhaler (Novolizer). modified pearl mill used milling fluid propellant. Furthermore, spray drying procedure established using novel process atomisation drying. Adhesive mixtures lactose 5-20% micronised cetrorelix-acetate were prepared. Analysis laser light scattering, HPLC, Karl Fischer, cascade impactor scanning electron microscopy performed characterise manufactured powders. Both procedures succeeded producing small range distributions, suitable deep lung deposition (D50 = 1.6 microm 3.3 drying). milled showed promising results when delivered Novolizer: reproducible highly efficient dispersion achieved (around 60% aerosolised < 5 microm). dried not processed adhesive mixture.