title: Impact of feed counterion addition and cyclone type on aerodynamic behavior of alginic-atenolol microparticles produced by spray drying.
abstract: The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) and systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration. In a previous work, atenolol was combined with alginic acid (AA) and microparticles were developed using spray-drying (SD) technology. Different AA/atenolol ratios, total feed solid content and operative variables were previously explored. In order to improve particle quality for inhalatory administration and the SD yield, in this work the AA acid groups not neutralized by atenolol were kept either free or neutralized to pH∼7 and two different SD cyclones were used. Particle morphology, flow properties, moisture uptake and in vitro aerosolization behavior at different pressure drops were studied. When the AA acid groups were neutralized, particle size decreased as a consequence of the lower feed viscosity. The SD yield and in vitro particle deposition significantly increased when a high performance cyclone was employed, and even when lactose carrier particles were not used. Although the in vitro particle deposition decreased when the storage relative humidity increased, the developed SD powders showed adequate characteristics to be administered by inhalatory route up to storage relative humidities of about 60%.
authors.affiliation: Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, UNS, San Juan 670, 8000 Bahía Blanca, Argentina.
authors.forename: Nazareth Eliana
authors.initials: NE
authors.lastname: Ceschan
authors.affiliation: Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Ingeniería Química, UNS, Avenida Alem 1253, 8000 Bahía Blanca, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Bucalá
authors.affiliation: Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET - Universidad Nacional del Sur (UNS), Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, UNS, San Juan 670, 8000 Bahía Blanca, Argentina. Electronic address: vrrigo@plapiqui.edu.ar.
authors.forename: María Verónica
authors.initials: MV
authors.lastname: Ramírez-Rigo
authors.affiliation: College of Pharmacy, The University of Texas at Austin, 2409 West University Avenue, Austin, TX, United States.
authors.forename: Hugh David Charles
authors.initials: HD
authors.lastname: Smyth
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000464:Alginates / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry; D001262:Atenolol / Q000008:administration & dosage* / Q000737:chemistry; D003890:Desiccation; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005612:Freeze Drying; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000737:chemistry; D008168:Lung / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011208:Powders; D011312:Pressure; D014783:Viscosity
chemical_list: D000336:Aerosols; D000464:Alginates; D000959:Antihypertensive Agents; D006603:Hexuronic Acids; D011208:Powders; D001262:Atenolol; D020723:Glucuronic Acid; D007785:Lactose
keywords: Atenolol; In vitro deposition; Inhalatory administration; Ionic interaction; Spray-drying