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Plenary: Multiphase flow enigmas in inhalation delivery

Rogueda, P (IDD - Novartis Horsham Res Centre)
Monday 05 January 2009, 14:00-14:40

Seminar Room 1, Newton Institute


The delivery of drugs to the lungs relies on multiphase flows, that are in want of being understood. Inhalation products, those intended for the treatment of Asthma for instance, are based on complex mixtures of cohesive fine particles (typically 1 to 5 ým). The interactions between the particles, and as a consequence their flow properties, are poorly understood and have rarely been modelised. 3 examples of inhalers will be reviewed to illustrate the problems encountered: -a pMDI (pressure metered dose inhaler), a product based on a drug suspension in a pressurised non aqueous propellant, -a passive DPI (dry powder inhaler), based on a particle mixture whose aerosolisation is triggered by the patient inhalation, -an active DPI, similar to a passive DPI, although in this case aerosolisation is provided by the vibration of a piezo-electric crystal, and trough what is known as synthetic jetting. Sedimentation/creaming profiles in pMDIs give rise to a rather odd phenomenon of surface reflux. In passive DPIs the difficulty is to understand the point of fluidisation of the powder bed in relation to particulates interactions. In active DPIs the issue is to understand how the energy for dispersing the powder, in this case the energy transmitted from a piezo-electric crystal, leads to aerosolisation. The 3 issues highlighted will serve as examples to highlight the need of understanding powder flows in the pharmaceutical formulation industry. Some attempts have been made to elucidate interaction mechanisms, mostly through measurements via AFM (atomic force microscopy) and powder rheology, but as will be shown there is a need to tie up what could be seen as coincidental measurements with deterministic models.


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