title: Development of a novel dry powder inhalation formulation for the delivery of rivastigmine hydrogen tartrate.
abstract: The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of L-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth-surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 °C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPF<5 μm), and lower mass median aerodynamic diameter (MMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation.
authors.affiliation: Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bss, sl15, Rio de Janeiro, RJ 21941-902, Brazil; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Alice
authors.initials: A
authors.lastname: Simon
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Amaro
authors.affiliation: Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bss, sl15, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Lucio Mendes
authors.initials: LM
authors.lastname: Cabral
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. Electronic address: healyam@tcd.ie.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
authors.affiliation: Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bss, sl15, Rio de Janeiro, RJ 21941-902, Brazil.
authors.forename: Valeria Pereira
authors.initials: VP
authors.lastname: de Sousa
mesh_terms: D000280:Administration, Inhalation; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D007785:Lactose / Q000737:chemistry; D007930:Leucine / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D018696:Neuroprotective Agents / Q000737:chemistry; D010316:Particle Size; D033362:Powder Diffraction; D000068836:Rivastigmine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D018696:Neuroprotective Agents; D007930:Leucine; D007785:Lactose; D000068836:Rivastigmine
keywords: Dry powder inhaler; Particle engineering; Rivastigmine hydrogen tartrate; Spray drying; l-Leucine