Sonocrystallisation of sodium chloride particles for inhalation

Fine sodium chloride particles are of pharmaceutical interest in aerosol delivery for diagnosis of asthma and bronchial related disorders. In this paper, stable NaCl particles with size ranging from approximately 1 mu m to sub-micron range were achieved by sonocrystallisation. The effects of sonocrystallisation temperature, ultrasonic power output and salt concentration were investigated in the ranges of 5-35 degrees C, 22-60 W and 8-34 g/100 g water, respectively, under a fixed ultrasonic frequency of 20 kHz. Size and morphology characterisation of particles were undertaken using laser diffraction and scanning electron microscopy. Optimally prepared particles were spray dried followed by in vitro impaction test for inhalation efficiency determination using an Aeroliser(R). Optimal conditions of temperature (< 5 degrees C), ultrasonic power output (similar to 35 W) and salt concentration (similar to 32 g/100 g water) exist that reduced the size of the crystals to the sub-micron scale. Spray drying increased the size of the prepared particles and altered the cubic shape to more rounded morphology. The fine particle fraction (based on recovery) was improved from approximately 12 to 34% when dispersion air flow rate was increased from 60 to 120 L/min. Sonocrystallisation represents an effective method for the preparation of NaCl particles suitable for pharmaceutical inhalation. The main advantage of this method is that it is rapid, simple and produces small crystal NaCl particles suitable for inhalation. (C) 2007 Elsevier Ltd. All rights reserved.