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

Abstract

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.

Keywords:

• Gas microbubbles
• spray drying
• inhalable particles
• aerosolization
• sodium cromoglycate

Disclosure of interest statement

All of the authors declare that they have no conflict of interest.

Additional information

Funding

The authors express their gratitude for the financial support granted by the [Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)] under Grant [PIP 11220150100704CO], the [Universidad Nacional del Sur (UNS)] under Grant [PGI 24/B252] and the [Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT)] under Grant [PICT-2016-1827].