Air classifier technology (ACT) in dry powder inhalation: Part 4. Performance of air classifier technology in the Novolizer® multi-dose dry powder inhaler

In this study, the in vitro fine particle deposition from a multi dose dry powder inhaler (Novolizer®) with air classifier technology has been investigated. It is shown that different target values for the fine particle fraction (fpf < 5 μm) of the same drug can be achieved in a well-controlled way. This is particularly relevant to the application of generic formulations in the inhaler. The well-controlled and predictable fpf is achieved through dispersion of different types of formulations in exactly the same classifier concept. On the other hand, it is shown that air classifier-based inhalers are less sensitive to the carrier surface and bulk properties than competitive inhalers like the Diskus®. For 10 randomly selected lactose carriers for inhalation from four different suppliers, the budesonide fpf (at 4 kPa) from the Novolizer® varied between 30 and 46% (of the measured dose; R.S.D. = 14.2%), whereas the extremes in fpf from the Diskus® dpi were 7 and 44% (R.S.D. = 56.2%) for the same formulations. The fpf from a classifier-based inhaler appears to be less dependent of the amount of lactose (carrier) fines (<15 μm) in the mixture too. Classifier-based inhalers perform best with coarse carriers that have relatively wide size distributions (e.g. 50–350 μm) and surface discontinuities inside which drug particles can find shelter from press-on forces during mixing. Coarse carrier fractions have good flow properties, which increases the dose measuring accuracy and reproducibility. The fpf from the Novolizer® increases with increasing pressure drop across the device. On theoretical grounds, it can be argued that this yields a more reproducible therapy, because it compensates for a shift in deposition to larger airways when the flow rate is increased. Support for this reasoning based on lung deposition modelling studies has been found in a scintigraphic study with the Novolizer®. Finally, it is shown that this inhaler produces a finer aerosol than competitor devices, within the fpf < 5 μm, subfractions of particles (e.g. <1, 1–2, 2–3, 3–4 and 4–5 μm) are higher.