Development of porous spray-dried inhalable particles using an organic solvent-free technique

Abstract

A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials. A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance.