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

• Published in: Powder technology Vol. 342; pp. 642 - 652
• Main Authors: Gallo, Loreana, Verónica Ramírez-Rigo, M., Bucalá, Verónica
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 15-01-2019; Elsevier BV
• Subjects: Air intakes; Air temperature; Ammonium; Ammonium bicarbonate; Aqueous solutions; Bicarbonates; Dissolution; Drug development; Friability; Hygroscopicity; Inlet temperature; Moisture content; Morphology; Particle size; Particle size distribution; Pore formation; Porous inhalable particles; Porous materials; Powder; Powder metallurgy; Process parameters; Shelf life; Size distribution; Sodium; Sodium cromoglycate; Solvent-free technique; Solvents; Spray drying; Spray forming; Stability analysis; Tap density; Water content; Spray drying; sodium Cromoglycate; Porous inhalable particles; Ammonium bicarbonate; Solvent-free technique
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2018.10.041

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.
Large porous inhalatory spray-dried particles obtained without using organic solvents and employing ammonium bicarbonate as pore forming agent. [Display omitted]
•Development of spray-dried inhalable porous particle without using organic solvents.•Cromoglycate porous particles with adequate in vitro aerosolization properties.•Appropriate long term stability of porous Cromoglycate inhalable particles.•Stable porous Cromoglycate inhalable particles even under mechanical stress.