Study of ageing of dry powder inhaler and metered dose inhaler by atomic force microscopy

Investigation by atomic force microscopy (AFM) is necessary for the analysis of the interaction between grains of powder used in dry powder inhalers (DPIs) in controlled atmosphere and metered dose inhalers (MDIs) in liquid phase. Measurements of nanonewton forces leading the powder cohesion resulting between active substances were performed. We have developed a protocol based on standard analysis: Scanning Electron Microscopy (SEM) and nano-analysis. This paper deals with the direct analysis of morphology evolution performed over three months in controlled atmosphere at various relative humidities (RH) and temperatures for DPIs and in a mimetic HFA134a liquid for MDIs in order to understand the behaviour of a binary mixing. Atomic force microscopy was also employed to characterize the interactions between particles.In this study, colloid probe AFM has been used to measure adhesive forces between drug particles in a controlled atmosphere for DPIs and in a liquid medium for MDIs. A link connecting the colloidal powder quality and particle–particle interactions is extracted from this study.

Graphical AbstractAgeing of two pharmaceutical compounds stored in various conditions (temperature and relative humidity) in air and in HPFP (HexaPerFluoroPentane) was followed until 90 days using AFM techniques in order to check variation of interparticular forces thanks to functionalised probes. In every condition, an important decrease of all types of interactions during the first thirty days has been recorded followed by a stabilisation of the forces.Figure optionsDownload full-size imageDownload as PowerPoint slide