A comparative analysis of techniques for characterizing particle-scale adhesion and cohesion

The dynamics of cohesive particles and their tendency to adhere to surfaces present significant challenges in various industrial processes. A profound understanding of adhesive and cohesive forces is crucial for the optimized design of continuous manufacturing systems, aiming to effectively mitigate flow-related issues such as blockages, segregation, irregular flow patterns, and flooding. In this study, the adhesive forces of eight excipients using four distinct methodologies were systematically evaluated, i.e., colloidal atomic force microscopy, contact angle measurement, drop tester, and centrifugation for comparative analysis. Qualitative assessments of cohesion, including the angle of repose, rotating drum, Carr index, and Hausner ratio were additionally implemented to corroborate the findings. By evaluating these methodologies in conjunction, the strengths and limitations of each approach can be explored. This comparison paves the way for a more nuanced understanding of particle adhesion dynamics and can aid in selecting the most suitable technique for specific applications.

Highlights

• Four distinct particle-scale adhesion measurement techniques were quantitatively compared.
• Particle-scale adhesion measurement were assessed against bulk scale cohesion characterization of eight excipients.
• The strengths and limitations of each technique were evaluated, which aids in process design.
• Colloid-AFM offers detailed insights into particle-scale adhesion, cohesion, surface roughness, and mechanical properties.

Introduction

Continuous manufacturing has received significant interest from the pharmaceutical companies in recent years [1]. Industries are changing their strategies from traditional batch processes to continuous manufacturing for reducing carbon footprint [2]. In this transition from batch to continuous processing, challenges arise with the flow of cohesive particles and their tendency to adhere to walls or particles, leading to increased budgets that must be carefully addressed. The flow behavior of particles is greatly influenced by cohesive and adhesive forces, with particle size and shape playing a crucial role in determining these forces [3]. Thus, knowledge of these forces is necessary to better design continuous manufacturing so that the flow problems (flow obstructions, segregation, irregular flow, flooding, etc.) can be magnificently mitigated [4].

Adhesive force is the pull-off force needed to remove adhering object from the contact area, mainly contributed by Van der Waals (VdW), interlocking, electrostatic and capillary forces [5]. The characterization of adhesion is challenging and varied, in which the centrifugation [[6], [7], [8]], drop tester [9] and colloid- Atomic Force Microscopy (AFM) [10,11] are the most frequently reported methods. The centrifugation method utilizes centrifugal force to separate adhering particles from a substrate surface under different rotation speeds, which is simple and has a wide availability of equipment. However, a small variation in particle size will lead to high variations in the calculated centrifugal force, and consequently also in the adhesion force derived thereof [7]. Drop tester is to obtain the resistance of particles to detach from the particle or wall in response to impact forces acting on the particle or wall [9]. Colloid-AFM is single particle interaction characterization by utilizing force directly on the particle under the monitor of microscopy to obtain the force-distance curve through the force sensor. However, it is being questioned by its time-consuming and expensive instrument cost [12].

Contact angle and Inverse gas chromatography- surface energy analyzer (IGC-SEA) are two alternatives to obtain the surface energy, and indirectly to obtain the adhesive force. Contact angle measurement is used to characterize the angle between the solid surface and the liquid drop surface while passing through the air-liquid-solid interface [13,14]. However, it relies on the consistency of the tangent contact line from the operator, which is hard to maintain. The method is not applicable for samples with irregular shapes and varying surface area [15]. IGC-SEA is to quantify the reversible gas-solid adsorption by packing a sample of powder or fibers into a gas-chromatography column [16]. IGC-SEA measures the adsorption behavior of volatile probes of known properties such as the Lifshitz – van der Waals component of surface free energy as well as the Lewis acid and Lewis base parameters for material surfaces on the solid unknown surface [17]. However, the experiment time for doing a sample in IGC-SEA takes hours and pre-surface area Brunauer-Emmett-Teller Method (BET) measurement is needed, and toxic solvents such as N-decane, n-nonane, n-octane, and n-heptane are usually utilized [18].

Similarly, cohesive force is focusing on the inner-interaction of the same material, and is stronger than gravity force as the particle size decreases. Bulk cohesion is highly related to the flowability of particles [19,20]. Rotating drum utilizes the free surface flow test under dynamic avalanching condition, contrary to shear testers, where a powder bed is subjected to a compressive load and the resistance to shearing is measured [21]. The angle of repose [22] measures the angle of inclination of the free surface to the horizontal of a free-standing pile, which angle of repose indicates the interparticle friction of bulk particles [23]. These two are indirect cohesion measurements qualitatively. Colloid- AFM, differently, direct quantitively measure the cohesive force between particles and obtains surface roughness which providing fruitful information. Carr index and Hausner ratio are calculated from the measurement of tap and bulk density of powder by using powder density analyzer. These two indicators are indirect representations of properties of cohesive particles.

Building on the introduction of various adhesion measurement techniques, it’s crucial to establish a comprehensive framework that aids in selecting the most suitable technique for specific industrial applications. However, the appropriateness of various measurement techniques has received insufficient consideration, which usually leads to inaccurate characterization of cohesive and adhesive forces for specific objectives. Thus, in this work, we strive to provide a correlation of adhesion and cohesion to the size, shape and flowability of the various materials from four different adhesion measurements and four different cohesion measurements. This endeavor marks a pivotal step towards optimizing manufacturing processes by integrating the most accurate and efficient adhesion measurement methods available.

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Materials

FlowLac100 is produced by spray-drying a suspension of fine milled alpha-lactose monohydrate crystals in a lactose solution. GranuLac200 consist of fine, sharp-edged lactose particles, is produced from milling. InhaLac120 is a sieved lactose suitable for dry powder inhalation. InhaLac150 is a milled lactose also suitable for dry powder inhalation. Tablettose100 is manufactured by a continuous spray agglomeration process. Meggle provided these excipients.

Leqi Lin, Mingzhe Yu, Yang Liu, Xizhong Chen, Zheng-Hong Luo, A comparative analysis of techniques for characterizing particle-scale adhesion and cohesion, Powder Technology, 2024, 120203, ISSN 0032-5910, https://doi.org/10.1016/j.powtec.2024.120203.

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