Hartmuth Schroettner

Preparation and characterization of physically modified glass beads used as model carriers in dry powder inhalers

The aim of this work is the physical modification and characterization of the surface topography of glass beads used as model carriers in dry powder inhalers (DPIs). By surface modification the contact area between drug and carrier and thereby interparticle forces may be modified. Thus the performance of DPIs that relies on interparticle interactions may be improved. Glass beads were chosen as model carriers because various prospects of physical surface modification may be applied without affecting other factors also impacting interparticle interactions like particle size and shape. To generate rough surfaces glass beads were processed mechanically by friction and impaction in a ball mill with different grinding materials that were smaller and harder with respect to the glass beads. By varying the grinding time (4 h, 8 h) and by using different grinding media (tungsten carbide, quartz) surfaces with different shades of roughness were generated. Depending on the hardness of the grinding material and the grinding time the surface roughness was more or less pronounced. Surface roughness parameters and specific surface area were determined via several complementary techniques in order to get an enhanced understanding of the impact of the modifying procedure on the surface properties of the glass beads.

Influence of surface characteristics of modified glass beads as model carriers in dry powder inhalers (DPIs) on the aerosolization performance

Abstract The aim of this work is to investigate the effect of surface characteristics (surface roughness and specific surface area) of surface-modified glass beads as model carriers in dry powder inhalers (DPIs) on the aerosolization, and thus, the in vitro respirable fraction often referred to as fine particle fraction (FPF). By processing glass beads in a ball mill with different grinding materials (quartz and tungsten carbide) and varying grinding time (4 h and 8 h), and by plasma etching for 1 min, glass beads with different shades of surface roughness and increased surface area were prepared. Compared with untreated glass beads, the surface-modified rough glass beads show increased FPFs. The drug detachment from the modified glass beads is also more reproducible than from untreated glass beads indicated by lower standard deviations for the FPFs of the modified glass beads. Moreover, the FPF of the modified glass beads correlates with their surface characteristics. The higher the surface roughness and the higher the specific surface area of the glass beads the higher is the FPF. Thus, surface-modified glass beads make an ideal carrier for tailoring the performance of DPIs in the therapy of asthma and chronically obstructive pulmonary diseases.

Crystallization speed of salbutamol as a function of relative humidity and temperature

Spray dried salbutamol sulphate and salbutamol base particles are amorphous as a result of spray drying. As there is always the risk of recrystallization of amorphous material, the aim of this work is the evaluation of the temperature and humidity dependent recrystallization of spray dried salbutamol sulphate and base. Therefore in-situ Powder X-ray Diffraction (PXRD) studies of the crystallization process at various temperature (25 and 35 °C) and humidity (60%, 70%, 80%, 90% relative humidity) conditions were performed. It was shown that the crystallization speed of salbutamol sulphate and base is a non-linear function of both temperature and relative humidity. The higher the relative humidity the higher is the crystallization speed. At 60% relative humidity salbutamol base as well as salbutamol sulphate were found to be amorphous even after 12 h, however samples changed optically. At 70% and 90% RH recrystallization of salbutamol base is completed after 3 h and 30 min and recrystallization of salbutamol sulphate after 4h and 1h, respectively. Higher temperature (35 °C) also leads to increased crystallization speeds at all tested values of relative humidity.