The relationship between physical properties of lactose monohydrate and the aerodynamic behaviour of adhered drug particles

The influence of particle size, shape, particle surface roughness and water loss on drying of lactose monohydrate carrier particles on the aerodynamic properties of dry powder inhalations based on interactive mixtures with a micronized drug has been investigated. Two sets of mixtures were prepared to relate the physical properties of the lactose monohydrate particles to the aerodynamic properties of the formulations: (A) constant mixing time and speed (25 min, 42 rev./min), and (B) optimal mixing time (speed 42 rev./min) to obtain a given adhesion force between drug and carrier particles. All ten lactose monohydrate batches provided different aerodynamic properties under test conditions (A) and (B). The relationship between the physical properties of the lactose monohydrate carrier particles and the aerodynamic properties of the drug is complex, and a simple interchange of the carrier material in terms of brand or grade appears impossible. Particle size, shape, water loss on drying, and to a lesser extent surface roughness influence the loss of drug for example in the device, preseparator and loss due to adhesion. The relationships can be quantified mathematically, if mixing has been undertaken under similar conditions, i.e. identical mixing time and speed (test condition (A)). However, for interactive mixtures, which have been manufactured under test condition (B), the connection between the physical properties of the carrier materials and the aerodynamic behaviour are less quantifiable. A similar adhesion force does not guarantee a similar aerodynamic behaviour of the drug in the cascade impactor. The findings indicate that it is mainly the site of adhesion, i.e. adhesion to fine or larger carrier particles which determines the drug lost in the device and preseparator, and is responsible for deviations in the MMAD. (C) 1998 Elsevier Science B.V.