Summary

Inhaled medicines are often formulated as adhesive mixtures, in which fine particles of the active pharmaceutical ingredient are attached to considerably larger carrier particles that aid handling and administration of the drug. Between them, a carrier and its adhered fines are commonly referred to as an adhesive unit. Information about adhesive mixtures can thus be inferred from studies of binary interactions between adhesive units. Such studies have recently been conducted with numerical methods for spherical, monodisperse fines in a velocity range that is representative of handling. In the present work, an attempt was made to try and understand how a complex shape of the fine particles affects the behavior of the adhesive units in terms of their integrity (stability ratio) and effective mechanical properties (coefficient of restitution) using discrete element method simulations. Fine particles of a tetrahedral shape were created from four partially overlapping spheres. Detailed discrete element method simulations of binary interactions between adhesive units was performed in a low velocity regime. It was observed that the shape of the fine particles has a considerable effect on the integrity and stability of adhesive units. Adhesive units with tetrahedral-shaped fines were more stable and had lower coefficients of restitution for the same impact velocity compared to systems with spherical fines of a similar size. Specifically, the losses were almost twice as large with spherical fines compared to the tetrahedral fines in a handling velocity regime. The obtained results provide further insights into the formulation and performance of adhesive mixtures for dry powder inhalers.

Key Message

Detailed discrete element method simulations of binary interactions between adhesive units indicate that the shape of the fine particles has considerable effects both on the mechanical properties and on the integrity of the adhesive units, thus providing further insights into formulation and performance of adhesive mixtures for dry powder inhalers.