Abstract
The Discrete Element Method (DEM) was used to investigate the mechanics of adhesive units, the building blocks of adhesive mixtures, formed by a randomised distribution of fine particles of different shape (spherical, tetrahedral and triangular bipyramidal) on the surface of spherical carrier particles. Binary collision between like adhesive units was simulated for different surface coverage ratios (SCRs; 0.5, 0.7 and 1) at a fixed surface energy (interfacial adhesion strength). The obtained data was analysed in terms of effective mechanical properties (restitution coefficients), physical stability of the adhesive units and redistribution of fines. The effect of the fine particle shape was predominant for low SCRs, and adhesive units formed from tetrahedral fines exhibited the largest physical stability. However, this effect diminished with increasing SCR, for which an extensive network of contact chains dominated the dynamics. These results point towards ways to improve the flowability and integrity of adhesive mixtures during handling.
Highlights
One of the increasingly popular ways for efficient delivery of drugs to the lungs is through dry powder inhalers (DPIs) [1]
Adhesive mixtures consist of a blend of large carrier particles (~100 μm aerodynamic diameter) and small micronised fine particles (< 5 μm aerodynamic diameter) of active pharmaceutical ingredient (API)
If rsph is the radius of a spherical fine, rtet is the radius of the tetrahedral particle, and rbip is the radius of the triangular bipyramid, the radius of microspheres could be represented by, rtet
Summary
One of the increasingly popular ways for efficient delivery of drugs to the lungs is through dry powder inhalers (DPIs) [1]. A special type of ordered mixture known as adhesive mixture is most commonly used for delivery of the active pharmaceutical ingredient (API) [2,3]. Adhesive mixtures consist of a blend of large carrier particles (~100 μm aerodynamic diameter) and small micronised fine particles (< 5 μm aerodynamic diameter) of API. An adhesive unit consists of fine particles adhered onto the surface of the carrier particle. APIs have a high surface to volume ratio and van der Waal's forces dominate the interaction producing a highly cohesive powder with poor flowability and a tendency to form agglomerates. Adhesive units prevent agglomeration of fine particles, improve flowability, maximise homogeneity and improve dispersibility of API during the process of aerosolisation [4]. Maintaining the integrity of these units during the process of handling is an important step to ensure the delivery of the drug load, and this is gaining increasing importance when dosage forms with higher drug loads are explored [5]
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