A dry powder inhaler (DPI) is a medical device used to deliver medication directly to the lungs. The DPI is a viscous mixture of a carrier and a drug. To reach the small airways located deep in the lungs, the aerodynamic diameter of the drug particles must be between 1 and 5 microns.
Particles of this size exhibit cohesion, poor flowability, and inefficient drug delivery. Therefore, carriers have been developed that allow drug attachment to the surface of larger, more fluid carrier particles (50–200 µm).
The interaction between the carrier and drug particles plays a crucial role in carrier-based dry powder inhalers (DPIs). On the one hand, this interaction must be strong enough to ensure drug adhesion to the carrier, thereby ensuring uniform drug delivery; on the other hand, this interaction must be weak enough to prevent drug detachment during inhalation.
This paper analyzes the effects of impact and friction on the physical processing of glass beads in a ball mill. Processing glass beads with finely dispersed hard abrasives creates extremely fine surface roughness, which can only be observed under high magnification, as shown in Figure 1.
Glass beads ranging in size from 400 to 600 microns were used. Tungsten carbide and quartz were used as grinding materials. For comparison, the Mohs hardness of soda-lime glass beads is approximately 6.
Tungsten carbide was supplied by Wolfram Bergbau und Huetten AG of St. Maarten, Austria, and quartz was supplied by Quarzwerke Austria GmbH of Melk, Austria.
The surface of glass beads was modified by friction and impact using a ball mill (Retsch S2 ball mill, Germany). The glass beads were ground with quartz powder and tungsten carbide powder at 424 rpm for 4 and 8 hours, respectively. The volume ratio of ground material to glass beads was 1:1.
After processing, the glass beads were rinsed multiple times with deionized water and dried in an oven at 150°C for 48 hours. The samples were stored in a desiccator until analysis.
Initially, nitrogen was used as the adsorbed gas for analysis, but due to the small specific surface area of glass beads of the specified size, satisfactory results were not achieved. Krypton was then used as the adsorbed gas for further analysis.
To compensate for the small specific surface area of glass beads and increase the absolute surface area, the sample tube was filled with glass beads. Thus, the average sample mass was approximately 12 grams of glass beads.
The analysis was performed using a Tristar II surface area and porosity analyzer (Micromeritics Instruments, Norcrox, USA). Seven-point analysis was performed at relative pressures ranging from 0.07 to 0.25, and the specific surface area was determined using the Brunauer-Emmett-Teller (BET) equation.
To examine the measurement results and ensure the accuracy of the instrument’s measurement of such a small surface area, we weighed a small amount of Micromeritics’ reference material, aluminum oxide, so that the absolute surface area was in the same range as the absolute surface area measured with glass beads.
By reducing the mass of the standard sample to approximately 0.5 g, it was possible to achieve an absolute surface area of 0.105 m², which is comparable to the absolute surface area of glass beads ranging in size from 0.09 to 0.2 m².
Despite the small size of the standard sample, the measurement results still showed a specific surface area of 0.24 ± 0.06 m2/g (mean, n=3 ± standard deviation), which is an acceptable value within the specified range (0.28 ± 0.03 m2/g).
Figure 2 shows an example of a standard BET specific surface area plot for aluminum oxide. Finally, the results demonstrate that the instrument provides reliable measurement results even outside the manufacturer’s specified measurement range.
Figure 2. BET specific surface area diagram of a standard aluminum oxide sample analyzed with krypton (10-point analysis was performed at relative pressures from 0.05 to 0.025, with a total mass of 0.5488 g).
Figure 3 shows the results of specific surface area measurements for untreated and physically modified glass beads. The beads treated with tungsten carbide for 8 hours had the highest specific surface area, while the beads treated with quartz for 4 hours had the lowest.
The specific surface area obtained by grinding with quartz for 8 hours and tungsten carbide for 4 hours lies between these two values. In fact, the specific surface area obtained by grinding with tungsten carbide for 4 hours is smaller than that obtained by grinding with tungsten carbide for 8 hours, while the specific surface area obtained by grinding with quartz for 8 hours is greater than that obtained by grinding with quartz for 4 hours. This result is consistent with the hardness of the material being ground and the processing time.
Gas adsorption proved to be a suitable tool for quantifying changes in the surface morphology/roughness of glass beads, even within the measurement range specified by the manufacturer.
The measured surface area corresponds to the abrasive hardness, processing time, and scanning electron microscopy (SEM) images. Reducing the mass of the standard sample demonstrates the feasibility of measuring extremely small surface areas.
Post time: Jan-14-2026