Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers.
Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 min) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 min, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs.
Department of Pharmacy, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy. Electronic address: francesca.buttini@unipr.it.
Francesca
F
Buttini
Department of Pharmacy, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Michele
M
Miozzi
Interdepartmental Center, Biopharmanet-TEC, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Anna Giulia
AG
Balducci
King's College London, Institute of Pharmaceutical Science, London SE1 9NH, UK.
Paul G
PG
Royall
Chiesi Farmaceutici Spa, Via Palermo 26, 43122 Parma, Italy.
Gaetano
G
Brambilla
Department of Pharmacy, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Paolo
P
Colombo
Department of Pharmacy, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Ruggero
R
Bettini
King's College London, Institute of Pharmaceutical Science, London SE1 9NH, UK.
Ben
B
Forbes
D000280:Administration, Inhalation; D000336:Aerosols; D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D058868:Compressed Air; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D000431:Ethanol / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry; D000068759:Formoterol Fumarate; D005990:Glycerol / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D007700:Kinetics; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D014783:Viscosity
D000336:Aerosols; D004983:Ethanolamines; D006845:Hydrocarbons, Fluorinated; D012997:Solvents; D000431:Ethanol; D001507:Beclomethasone; D005990:Glycerol; D000068759:Formoterol Fumarate
Beclomethasone dipropionate (BDP); Bioequivalence; Hydrofluoroalkane; Orally inhaled drug product (OIDP); Pressurised metered dose inhaler (pMDI)