Gas-phase synthesis of l-leucine-coated micrometer-sized salbutamol sulphate and sodium chloride particles

Coating of micrometer-sized particles of salbutamol sulphate or sodium chloride with the amino acid l-leucine in the gas phase is described. A novel method to synthesize core particles and coat them with l-leucine simultaneously was carried out in an aerosol flow reactor. The coating was prepared via temperature-induced heterogeneous nucleation of l-leucine vapor on the 0.6–1.0 µm core particles, and subsequent growth of l-leucine crystals by physical vapor deposition. The core salbutamol particles were amorphous, whereas the NaCl core particles were crystalline. The l-leucine sublimation that took place at 140–195 °C depended on the identity of the core material due to (i) molecular interaction and (ii) phase mixing. The former was dominant with salbutamol/l-leucine particles and the latter was dominant with NaCl/l-leucine particles. During the vapor deposition, l-leucine formed a discontinuous coating layer of leafy-looking crystallites, with sizes from a few nanometers to hundreds of nanometers, pointing out from the core particle surface. The l-leucine deposition properties depended on the core morphology: l-leucine crystallites were distributed more evenly on salbutamol core surfaces than on salt core surfaces, where the crystallites were localized mainly on edges. The stability of coated salbutamol particles was retained during storage under humid conditions.