(492b) Theoretical and Experimental Investigation into the Impact of Tribo-Charging on the Performance of Dry Powder Blends
AIChE Annual Meeting
Wednesday, November 13, 2019 - 8:21am to 8:42am
Powder charging is known to greatly affect the industrial processing and performance of particulate and granular materials. The underlying process of contact charging is referred to as tribo-electrification1. Pharmaceutical materials are usually insulators and often accumulate electrostatic charges that can detrimentally affect their processability1. Thus, tribo-electric charging can be expected to provide an important contribution to particle-particle and particle-wall interactions during handling and transport of powders of dielectric materials. It would therefore be desirable to systematically determine the factors that contribute to powder tribo-charging. Generally, the extent of tribo-charging is expected to be related to the difference between the work function (WF) values of the two contacting surfaces2. Other material properties relevant to tribo-charging include surface energy, hygroscopicity/wettability, surface roughness, and particle shape1. Therefore, it is anticipated that different materials as well as particulate properties will be crucial in the tribo-charging of different pharmaceutical blends. Finally, also, the effect of unit operations involved in the manufacturing of pharmaceutical products must be taken into account. Thus, it was the aim of our work to systematically understand the factors critically affecting this phenomenon, and its respective impact on formulation performance.
Design of the studies
Model pharmaceutical materials were selected and their material and particle properties characterized. Tribo-charging acquired during the flow over a stainless steel tube was investigated in order to obtain relevant information of their behavior during unit operations such as feeding, transport, blending and capsule filling etc. The results of relative charging in the materials were interpreted considering their distinct chemical and physical properties. More concretely, evaluation of the net charge of the different materials was carried out using GranuchargeTM (Granutools). Measurements were performed under defined environmental conditions. First, initial charge to mass ratio (q0) was recorded by dispensing the powder directly into a Faraday pail. In a consecutive step, the powder was transferred to a vibrating stainless-steel V-tube and the charge to mass ratio (q1) was recorded again after the powder was transported through the tube. The acquired charge during flow, thus charging tendency, was determined as Îq=q1-q0.
Tribo-charging trends predicted from first principles
The tribo-charging of five different pharmaceutical materials acetylic salicylic acid (Merck KGaA), Ibuprofen (Merck KGaA), Î±-lactose monohydrate (LH100, Meggle), trehalose (Cargill Deutschland GmbH), and D-Mannitol (P160C, Roquette) were experimentally investigated. In order to concentrate on the effect of electronic properties of the materials, other characteristics and experimental parameters, in particular the particle size (distribution) of the used powders, were kept identical for the five investigated materials. The measured tribo-charging trends were compared with the energies from electronic structure calculations.
It was found that varying the level of theory (from semi-empirical/PM6, over DFT/GGA, to DFT/meta-GGA) affects the correlation between tribo-charges and calculated energies only weakly. However, of the calculated values (highest occupied molecular orbital (HOMO), energy levels, vertical and adiabatic ionization potentials (IP), and work functions (WF)) only adiabatic IP values showed a useful correlation with tribo-chage, with a pearson correlation around r = 0.9. The calculated WF values however, the measure that is traditionally used for prediction of contact-electrification, showed a poor correlations with our experimental data. This unexpected result is presumably due to a combination of two facts: 1) experimental IP and WF values usually show a good correlation, and 2) the lowest unoccupied molecular orbital (LUMO) energy, which is used here to estimate electron affinity and for the calculation of the WF, is notoriously difficult to calculate accurately, this carrying over to the calculated WF values. We conclude that since the IP can be calculated more accurately, and it correlates with the WF, the IP can be used as a replacement for the WF, in particular if one is primarily interested in relative values. Although limited in number, our data suggests that electronic structure calculations can be used to estimate relative tribo-charging trends for pharmaceutical materials, provided that other material properties are comparable.
Tribo-charging trends of different particulate materials
Although prediction of tribo-charging trends using first principles is desirable to determine a priori the molecular properties affecting the contact of different materials, its applicability is still limited as it does not discriminate between different solid and particle states of materials (as discussed in the previous section). Therefore, the tribo-charging of different salbutamol sulphate (SBS) (Selectchemie) particles engineered using jet-milling (Spiral air Jet Mill 50 AS, Hosokawa Alpine AG) and spray-drying (Nano spray-dryer B-90, Büchi) was experimentally investigated and compared4.
It was demonstrated that different surface chemistries arising from distinct solid-states of the same material, different contact areas due to particle properties like shape, size and morphology, as well as variable water contents can critically impact the polarity and magnitude of tribo-charging. Amorphous, spherical shaped SBS particles with a high water content (generated via spray-drying) attained positive charge of a higher magnitude. In contrast, the milled fine particles with irregular shape and lower water content tended to charge negatively and to a lower extent4.
Tribo-charging trend of different material blends
To understand how different particulate characteristics can affect the tribo-charging of pharmaceutical powder blends, the distinctly engineered fine particles of SBS (1-5 µm) were mixed with coarse D-mannitol (about 100 µm) (MAN) at 2 drug loadings (2 wt% and 5 wt% of SBS). Likewise, the tribo-charging of the obtained powder blends was evaluated4.
Comparison of the two crystalline powders (jet-milled SBS and MAN) revealed that theoretically calculated WFs can provide a rank order of the sign of charge when the materials were in contact with metal, supporting our previous conclusions that electronic structure calculations can be used to estimate relative tribo-charging trend. Concerning the charging tendency of the powders blends, an increased charge mitigation effect was observed when a higher concentration of fine SBS particles were blended with the coarse MAN. Likewise, it was found that the charging tendency of the coarse particles is less relevant when blended with fine materials. Consequently, it was possible to conclude that evolution of charge in the blend seemed to be dominated by the nature of fines and their concentrations contributing to inter-particle contacts4.
Tribo-charging trends arising from distinct process parameters
In a final step, powder blends have to be processed into a final dosage form to be administered to the patient. Capsules are one of the most common solid oral and inhalation dosage forms. Therefore, the capsule filling process was selected to investigate the impact that processability can have on the tribo-charging. For that, size 3 gelatin (Quali-GTM, Qualicaps) as well as thermally (Vcaps® Plus, Capsugel) and chemically gelled HPMC capsules (Quali-V®-I, Qualicaps) were filled (Labby, MG2) targeting distinct fill weights (25 and 75 mg) and the effect on tribo-charging was evaluated and compared5.
Comparing the charge tendency of the different capsules, it was seen that gelatin (Gel-Cap) and the thermally gelled HPMC (TG-HPMC-Cap) capsules showed a higher tendency to acquire charge during contact with stainless steel than chemically gelled HPMC (CG-HPMC-Cap). When different fill weights were used, it was observed that the Gel-Cap and TG-HPMC-Cap had a decreased tendency to acquire charge as the powder fill level increased. In contrast, the powder fill level had negligible impact on the charging properties of CG-HPMC-Cap capsules. This revealed the similar charging tendencies of capsules manufactured with different materials and the dissimilarity between capsules of the similar material5.
Tribo-charging is a complex and very relevant phenomenon that is still largely unpredictable. In this work, we propose a bottom-up approach to the understanding of tribo-charging trends of pharmaceutical materials. From molecular properties to particulate and powder bulk characteristics to the influence of process conditions on tribo-charging, providing a systematic understanding the factors critically affecting this phenomenon, and its respective impact on dry powders performance.
1 Wong J, Kwok PCL, Chan HK. Electrostatics in pharmaceutical solids. Chem Eng Sci. 2015; 125:225-237.
2 Helmholtz H. Studien über electrische Grenzschichten. Ann der Phys und Chemie. 1879; 243(7):337-382.
3 Brunsteiner M, Zellnitz S, Pinto JT, Karrer J, Paudel A. Can we predict trends in tribo-charging of pharmaceutical materials from first principles?. Powder Tech. 2019; Submitted.
4 Zellnitz S, Pinto JT, Brunsteiner M, Schroettner H, Khinast J, Paudel A. Tribo-charging behaviour of inhalable mannitol blends with salbutamol sulphate. Pharm Res. 2019; Accepted.
5 Wutscher T, Zellnitz S, Kobler M, Buttini F, Andrade L, Daza V, Mercandelli A, Biserni S, Probst SE, Khinast J, Paudel A. Influence of Storage Humidity and Powder Fill Level on Charging Behaviour of Different Capsules Types. RDD Europe 2019; Lisbon, Portugal.