Preparation of inhalable salbutamol sulphate using reactive high gravity controlled precipitation.

Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Physical properties of the powders were characterised by scanning electron microscopy, X-ray powder diffraction, thermal gravimetric analysis and dynamic water vapour sorption. Aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The results showed that the reactive HGCP powder, comprising primary SS sub-micron particles (approximately 100 nm in width and approximately 500 nm in length) packed into loose spherical agglomerates of about 2 microm in diameter, is of the same polymorphic form as the raw crystalline material, has a high specific surface area (24.7 +/- 0.1 m(2)/g), but a low moisture content (0.2%) and low moisture uptake (1.4% at RH 90%). The aerosol performance of the reactive HGCP powder is excellent, showing FPF(loaded) and FPF(emitted) of 76 +/- 5% and 83 +/- 7%, respectively, with low capsule and device retention. In conclusion, reactive HGCP followed by spray drying is suitable to produce stable crystalline powders of salbutamol with enhanced inhalation properties.