Containment: How novel bench top systems allow the evaluation of dustiness during tableting

In recent years, the number of highly active pharmaceutical ingredients (HPAPIs) has significantly increased resulting in a high interest of pharmaceutical manufacturers in the safe handling of these hazardous compounds. Necessary precautions include containment strategies such as establishing airlocks, maintaining pressure differentials, using high-efficiency filters, as well as the use of specialized personnel-protective equipment to reduce health risks. In the context of containment, the dustiness of pharmaceutical powders represents a challenge. Therefore, to predict the dustiness of HPAPIs, two novel two-chamber setups were developed both consisting of an emission and a detection chamber. In one of them the chambers were separated by a controllable flask allowing the examination of dust emissions under plain diffusive flow as well as under oppositely directed convective flow. The other setup was equipped with defined measuring points (IOM samplers) to obtain stationary exposure data on dust formation as well as information on the spatial dust distribution of pharmaceutical powders. It was demonstrated that the newly developed chamber setups are capable of reproducible aerosolization of the surrogate powder acetaminophen. A high reproducibility of the dust emissions was observed as confirmed by low standard deviations and a linear correlation between the atomized amount of acetaminophen and the resulting dust emissions. Furthermore, the first chamber setup was proven to be suitable for the investigation of the dust emission at different flow conditions (plain diffusive transport and diffusive transport with an oppositely directed convective flow of airborne particles). Particularly the pronounced influence of the oppositely directed convective flow on the dust emissions indicates that an increase of the pressure difference between the emission and the detection chamber led to a major reduction of the dust emissions. The results with the second chamber setup showed, that the spatial distribution of aerosolized acetaminophen within the detection chamber could be investigated and analyzed via IOM samplers: a linear relationship between the amount of sample applied and the settled amount of acetaminophen within the IOM samplers was demonstrated. In addition, the results showed that the distribution of the aerosol could be observed in the horizontal axis and the sedimentation in the vertical axis of the defined measuring points. In summary, the novel chamber setups offer multiple measuring options for the investigation of the dustiness of powders and will provide even more insight into containment issues in future investigations.