Insight into the dust explosion hazard of pharmaceutical powders in the presence of flow aids

Highlights

• Improvement in dust flowability can cause apparent reductions in MIEs of APAP and MCC.

• Explosion parameters including MIT, MEC and P_max are independent of dust flowability.

• Flow aids added to mixtures can also be regarded as dispersion improvement additives.

• Formation of dust clouds depends on both powder properties and boundary conditions.

• Particle interaction is the decisive factor behind the connection between dust flowability and explosion hazard.

Abstract

Coating of nanoscale flow aids is widely used in pharmaceutical applications to increase the flowability of cohesive powders. For combustible pharmaceutical active ingredients and excipients, it is unclear whether increased flowability affects the dust explosion hazard. In this work, acetaminophen (APAP) and microcrystalline cellulose (MCC) were studied with and without a coating of silica nanoparticles. A full set of explosion parameters for the pure materials and their flow-improved mixtures was determined in accordance with ASTM standards. The results show that parameters including minimum ignition temperature, minimum explosible concentration, and maximum explosion pressure were independent of powder flow properties, while the presence of flow aids led to significantly lower minimum ignition energy values for both APAP and MCC, and a slightly higher maximum rate of pressure rise for APAP. The connection between dust flowability and the dust explosion hazard is discussed with respect to these experimental results.

Introduction

Powdered materials are extensively handled in the pharmaceutical industry. Nowadays, most active pharmaceutical ingredients and their excipients are fine powders with particle size of 100 μm or lower. These micronized powders pose new challenges in processing, including handling difficulties (Sharma and Setia, 2019) and the dust explosion hazard associated with decreased particle size (Maniar et al., 2020).

Fine particles tend to agglomerate, segregate, compress, and react with moisture, all of which decrease flowability (Sharma and Setia, 2019). Poor flowability in turn adversely affects several pharmaceutical operations such as blending, sieving, grinding, die-filling, and tableting, which can reduce quality of the final product (Jallo et al., 2012). To improve flow properties, small amounts of flow aids or glidants are often added, thereby easing the handling of these fine powders. For example, silica nanoparticles show promise in improving flowability of fine pharmaceutical powders via surface modification (Sharma and Setia, 2019; Jallo et al., 2010, 2012; Tran et al., 2019; Kojima and Elliott, 2013; Yang et al., 2005; Zhou et al., 2012; Kunnath et al., 2021; Han et al., 2011; Ghoroi et al., 2013a, 2013b). The fact that inter-particle interactions like van der Waals, capillary, and electrostatic forces increase as particle size decreases is well established. Once the attraction forces between particles exceed gravitational forces, powders exhibit cohesiveness and poor flowability. For particles less than 30 μm, van der Waals interactions play a major role when particle surfaces are in contact or close proximity, resulting in a high degree of cohesiveness (Jallo et al., 2012; Eckhoff, 2009). When using nano-silica particles as flow aids, the basic idea is that the nano-silica (guest) particles uniformly adhere to the primary (host) particle surfaces, acting as nanoscale roughness and disrupting contact geometry or increasing the distance between host particles, thereby reducing the van der Waals forces (Sharma and Setia, 2019). Not only is flowability improved, but other properties such as bulk density, dispersibility, and dissolution ability can be favorably modified through this nanoparticle coating method (Jallo et al., 2012; Han et al., 2011; Ghoroi et al., 2013a, 2013b).

On the other hand, drug powders or pharmaceutical excipients are often combustible, which causes safety concerns for the industry. Explosion results in 89% of the fatalities reported in the pharmaceutical industry and combustible dust is implicated in about 20% of these explosion incidents (Maniar et al., 2020). To date, explosibility of many types of pharmaceutical ingredients are recognized (Dufaud et al., 2012; Sanchirico et al., 2015; Centrella et al., 2020), but the relationship between dust explosion hazard and powder flow performance has not been well studied.

In applications of energetic materials, the effect of flowability of aluminum powder on its reactivity was evaluated using constant volume combustion testing and thermo-gravimetric analysis for both untreated and surface modified aluminum powder (Jallo et al., 2010). It was reported that powders with increased flowability exhibited improved combustion characteristics if inert components were not added to the aluminum. Other studies in dust explosion field found enhanced ignitability parameters and flame propagation of organic or metallic dust, even though the additives were intrinsically non-combustible (e.g., nano-titania and nano-silica) (Janès et al., 2014; Bu et al., 2019, 2020). This phenomenon is mostly due to improved dispersion of combustible particles in a gas medium.

Mixing of combustible dust and oxidant is one of five essential prerequisites in the dust explosion pentagon. A sometimes overlooked fact is that particles originally in mutual contact can only be separated with difficulty and dispersed into primary particles during the formation of airborne dust clouds, particularly in the case of cohesive pharmaceutical powders (Eckhoff, 2009). The existence of unbroken particle agglomerates causes the actual particle size distribution (PSD) of a dust cloud to shift towards larger diameters, which limits the reactive surface area and lowers the explosion hazard. However, if the tendency for particles to agglomerate is reduced, for example, by introducing flow aids, the potential for a higher explosion hazard would occur. Since improved flowability via surface modification normally implies simultaneous improved dispersibility (Ghoroi et al., 2013b), this could in turn result in achieving a more de-agglomerated dust cloud. The possibility that changes in particle interaction brought about by the presence of flow aids are significant enough to increase the dust explosion hazard should therefore be investigated.

Fig. 1 illustrates the research objective of the current work. To clarify this issue, deflagration testing was conducted using common pharmaceutical powders with and without flow aids, following relevant ASTM standards at the Dust Explosion Lab of Dalhousie University, in an effort to provide insights into the correlation between dust flowability/dispersibility and dust ignitability/explosibility, from the perspective of researchers in dust safety community.