Influence of microbubbles on the production of spray-dried inhalable particles

The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sodium cromoglycate) was selected in order to evaluate the effect of different gases (air, CO2 and N2) and spray drying operating conditions on the particles aerosolization performance. To this end, gas supersaturated aqueous drug solutions were obtained in a pressurized vessel and then processed by spray drying. The process yield, morphology, size, bulk and tap densities, moisture content and aerosolization properties of the particles were evaluated. The presence of microbubbles in the spray drying feed led to powders with smaller mean geometric sizes than particles obtained without bubbles. The gas-water solubility emerged as a key parameter to obtain inhalatory particles with good aerosolization properties. High water-soluble gases led to bigger particles, while low soluble ones allow to produce smaller particles. The use of air (with an intermediate water solubility respect to CO2 and N2) and an adequate set of spray drying operating conditions allowed to obtain sodium cromoglycate particles with superior aerosolization properties than a commercial formulation. Overall, a novel, simple and low-cost method to produce inhalatory particles with excellent aerosolization properties was developed by supersaturating the spray drying liquid feed without using pore-forming agents during the production step, or carriers in the final formulation.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Serain, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Renaudo, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Lopez, Eduardo. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucalá, Verónica. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin