The morphology and various densities of spray dried mannitol

Abstract

This work describes characteristic parameters (size, shape, morphology, bulk and effective particle density) of mannitol carriers intended for pulmonary drug delivery which had been prepared at spray drying outlet temperatures of 67 °C (M67), 84 °C (M84) and 102 °C (M102). Scanning electron microscopy (SEM) images showed clear differences in surface roughness and shape of the spray dried products. At low outlet temperatures spherical, rough particles were obtained whereas higher drying temperatures resulted in particles with multiple surface indentations and a smoother surface. It was possible to analyze surface roughness with confocal-scanning microscopy and SEM tilted-image analysis. Mercury intrusion porosimetry (MIP) turned out to be a highly valuable experimental tool for the determination of the effective particle density. All spray drying conditions resulted in the formation of particles with a shell and a core. The core is either hollow or filled with mannitol crystals. The inner hollow space volume decreases with increasing temperature. For this reason particles prepared at higher temperatures exhibit a higher mechanical stability (M67: 2.46 ± 0.77 MPa; M84: 5.03 ± 1.51 MPa; M102: 11,75 ± 4,01 MPa). The products prepared at 67 °C showed the lowest bulk and effective particle densities. The effective particle densities were determined to be 0.832 ± 0.002 g/cm3 (M67), 1.004 ± 0.008 g/cm3 (M84) and 1.111 ± 0.011 g/cm3 (M102) respectively.