Single step bottom-up process to generate solid phospholipid nano-particles

Context: The particularity of the Nano Spray Dryer B-90 is the nozzle containing a mesh vibrating at ultrasonic frequency. Objective: To study process parameters and processability of crude phospholipid dispersions, in particular the effect of concentration and mesh aperture on both particle size of the dry solid phospholipid nano-particles and on the re-dispersed powder. Materials and methods: Phospholipid dispersions containing trehalose as a stabilizer were spray dried. Particle size distributions of dry powders were evaluated by SEM micrographs and by PCS and cryo-TEM for the re-dispersed particles. Results: Spray drying of crude liposome dispersions revealed solid phospholipid nano-particles. Aperture of nozzle mesh and concentration of the dispersions, respectively, both increased the size of solid phospholipid nano-particles. For crude dispersions, an upper limit with respect to processability was found close to below 10% (m/m) even if the crude dispersion was passed along the mesh several times; however, more effective dispersing methods such as pre-sonication can push the limit of processability to higher values. Discussion and conclusion: The nano spray dryer is capable of spray drying crude dispersions of phospholipids in concentrations below 10% (m/m) generating solid phospholipid nano-particles relevant for pulmonary delivery. Re-dispersion of spray dried powder reveals liposomes.