Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy

The dry powder inhalers (DPIs) consist, in the most cases, of ordered mixture where the particles adhesion results of interactions between the drug and the carrier. Generally, one step of production process is the micronization of the drug particles in order to reduce the size for ordered mixing optimization. But this operation is known to partially create an amorphous surface. In this case, surrounding storage conditions, like relative humidity (RH), are able to modify the percentage of amorphous drug surface. The aim of this study was to investigate surface reactivity, surface energy and direct force measurements by atomic force microscopy (AFM) between lactose (carrier) and zanamivir (drug) crystals references in various conditions of RH. Secondly, an amorphization of the drug surface was induced by humidity relative treatment in order to evaluate the consequences of the transition from crystal to amorphous phase. The study demonstrated that the amorphization of drug surface induces an increase of drug affinity with the carrier surface. Ex situ and in situ amorphization of zanamivir tend to reach the affinity measured between raw materials: carrier and micronized drug particles. AFM allowed adhesion force discrimination between the different forms of the drug particles and demonstrated the potential for investigating adhesion properties in DPI formulation. (C) 2002 Elsevier Science B.V. All rights reserved.