Conversion of nanosuspensions to dry powders by spray drying: a platform for the preparation of inhalation particles

M. Malamatari, M. Bloxham, S. Somavarapu, G. Buckton


Controlled agglomeration of nanoparticles to micron- sized clusters has been proposed as an approach to deliver nanoparticles to the lungs combining enhanced pulmonary deposition and bioavailability of the drug. Indomethacin nanoparticle agglomerates stabilised with different surfactants and embedded in a matrix former, suitable for administration by dry powder inhalers (DPIs), were prepared and characterised. Indomethacin nanosuspensions (~ 250 nm) were prepared using wet bead milling in the presence of various stabilisers (Pluronics F127, F68 and TPGS 1000) and were further spray dried after the addition of mannitol and L- leucine. Scanning electron microscopy images revealed the composite structure of the dry powders to be spherical assemblies of indomethacin nanocrystals embedded in mannitol and L-leucine. The nanoparticle agglomerates appear to be highly crystalline (γ- form of indomethacin) and exhibited enhanced dissolution profiles (> 90% of the drug released in 5 mins) compared to raw indomethacin (< 20 % released in 10 mins). According to aerodynamic assessment using the Next Generation Impactor (NGI), the fine particle fraction for the different formulation was 49- 62% and the mass median aerodynamic distribution < 3.45 μm. Preparation of nanoparticle agglomerates by coupling wet bead milling and spray drying can be used as industrially feasible formulation- based approach to deliver nanoparticles of poorly soluble drugs to the lungs.

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