Study of a low-dose capsule filling process by dynamic and static tests for advanced process understanding

Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology

“…According to the flow function coefficient and the cohesion values, Lactohale 100 has the best flowability, followed by Lactohale 200 and Lactohale 220, which exhibits poor flowability (Stranzinger et al 2017). As reported in our previous work (Stranzinger et al, 2018b), the Hausner ratio and the Angle of Repose, two alternative powder flowability indices followed the same trend for these lactose powders.…”

“…These grades are commonly used as carriers in inhalation therapies. Sieved Lactohale 100 and two milled powders, Lactohale 200 and Lactohale 220, were selected on the basis of previous research efforts of our group focusing on their processability in a low-dose capsule filling process (Stranzinger et al, 2017, Stranzinger et al, 2018b). In these studies a comprehensive bulk powder profiling was performed that aimed to understand the effect of material attributes on the capsule filling performance.…”

“…In the present study we applied this new terahertz-based method to analyze the correlation of the measured powder bed density with the fill weight in a capsule. This was performed by drawing small quantities from the powder bed using a novel sampling system that mimics the capsule filling process (Stranzinger et al, 2018b) in proximity to the rotating container. Hence, the relative density of the powder bed was monitored and correlated with off-line weight measurements to predict the fill weight based on the terahertz reflection measurement.…”

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

“…All experiments were carried out under controlled environmental conditions (T = 20-24 °C, 40-60% relative humidity). The following material attributes were determined in triplicate: the true density was measured with a helium pycnometer (AccuPac II 1340, Micromeritics, Norcross, USA); the bulk (BD) and tapped density (TD) values and the median particle size (x50) for the lactose excipients were measured previously for the same batch of material [44,45]. BD, TD values and the median particle size (x50) for SMCC excipients were taken from the technical data sheets (i.e., product sample certificate of analysis) provided by the supplier.…”

“…Lactose is commonly regarded as a predominately brittle material that breaks easily at relatively low deformation [54], whereas MCC is considered relatively ductile material that can undergo a significantly higher elastic and plastic deformation [54]. In previous studies [44,45], the three used grades of lactose excipients (Lactohale 100, Lactohale 200, Lactohale 220) were extensively characterized, including their bulk powder properties, flow properties and friction properties. In regard to MCC it is important to note that in our study silicified MCC (SMCC), a material produced by a process of 'silicification', was used.…”