In vitro characterisation of terbutaline sulphate particles prepared by thermal ink-jet spray freeze drying

Thermal ink-jet spray freeze-drying (TIJ-SFD) was used to produce inhalable particles of terbutaline sulphate, the aerosolisation properties of which were compared to the commercial Bricanyl® formulation. Scanning electron micrograph images showed the particles to be spherical, highly porous and suitable for aerosolisation from a simple, capsule-based dry-powder device (Cyclohaler®) without the need for additional excipients. Particle size was dependent upon the concentration of solution jetted, as well as the distance between the print head and the surface of the liquid nitrogen. Starting with a 5% (w/v) solution and maintaining this distance at 3 cm produced spherical, porous particles of volume median diameter (VMD) 14.1 ± 0.8 μm and mass median aerodynamic diameter (MMAD) 4.0 ± 0.6 μm. The fine particle fraction (proportion of aerosol with MMAD ≤ 4.46 μm) was 22.9 ± 3.3%, which compared favourably with that of the marketed dry powder inhaler formulation of terbutaline (Bricanyl® Turbohaler®; 25.7 ± 3.8%), tested under the same conditions. These findings show that TIJ-SFD is a useful tool to predict the viability of a DPI formulation during preformulation physicochemical characterisation.

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