title: Investigations on particle surface characteristics vs. dispersion behaviour of L-leucine coated carrier-free inhalable powders.
abstract: Aerosol microparticles of salbutamol sulphate are gas-phase coated with an amino acid L-leucine. Depending of the saturated state of L-leucine, the coating is formed by the surface diffusion of L-leucine molecules within a droplet or by the physical vapour deposition (PVD) of L-leucine or by the combination thereof. The PVD coated particles showed excellent aerosolization characteristics in a carrier-free powder delivery from an inhaler. The aerosolization of the fine powders is compared with surface energy parameters analysed by inverse gas chromatography (IGC). The dispersion testing is conducted by a Inhalation Simulator using a fast inhalation profile with inhalation flow rate of 67 l min(-1). It is found that the powder emission is affected by the morphology, surface roughness (asperity size and density) of the particles and acidity of particle surface. The latter affects the dispersion and dose repeatability of fine powder in a case if L-leucine content is high enough. However, there is no direct correlation between dispersive surface energies and aerosolization performances of the powders. Crucial factors for the improved aerosolization rely weakly on surface acid-base properties but strongly on particle morphology and fine-scale surface roughness.
authors.affiliation: NanoMaterials Group, Laboratory of Physics & Center for New Materials, Helsinki University of Technology, P.O. Box 5100, FI-02015 TKK, Finland. janne.raula@tkk.fi
authors.forename: Janne
authors.initials: J
authors.lastname: Raula
authors.forename: Frank
authors.initials: F
authors.lastname: Thielmann
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Esko I
authors.initials: EI
authors.lastname: Kauppinen
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007930:Leucine / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D007930:Leucine; D000420:Albuterol