Can ‘extrafine’ dry powder aerosols improve lung deposition?

Abstract

There is increasing interest in the use of so-called 'extrafine' aerosols to target the small airways in the management of asthma and COPD. Using previously presented deposition data, we assessed whether submicron (<1μm) particles can improve central and deep lung deposition. Our data show instead that particles in the range 1-3μm are much more relevant in this respect. Based on this finding the Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster (Fostair) NEXThaler ICS/LABA combination DPIs were tested in vitro as a function of the pressure drop (2, 4 and 6kPa) across the inhaler. Obtained fine particle fractions (FPFs) <5μm (as percent of label claim) were divided into subfractions <1, 1-3 and 3-5μm. Differences of up to a factor of 4 were found between the best (Turbuhaler) and worst performing DPI (Elpenhaler), particularly for the FPF in the size range 1-3μm. The NEXThaler, described as delivering 'extrafine' particles, did not appear to be superior in this size range. The marked differences in amount and size distribution of the aerosols between the devices in this study must cause significant differences in the total lung dose and drug distribution over the airways.

Impact of Inhalation Flow, Inhalation Volume and Critical Handling Errors on Delivered Budesonide/Formoterol Dose in Different Inhalers: An In Vitro Study

“…In that study, the flow rate ranges investigated were shifted upwards, 45-75 L/min for Easyhaler and 55-93 L/min for Turbuhaler, compared to the present study. The pharmacopeia standard test condition at 4 kPa was used as the medium flow rate and the low and high flow rates, equivalent to 2 and 6 kPa, respectively, were selected in accordance with De Boer et al [16]. The results in our study showed a similar FPD flow rate dependency between the three inhalers tested.…”

“…The DD from the Turbuhaler was similar, regardless if shaken or not. devices has been extensively studied [16,17]. For analogues to be approved in the European Union (EU), it is a prerequisite that the particle size distribution is similar to the originator product at three different flow rates: low, medium and high [18].…”

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

“…A similar trend was observed for EFPD (<3 μm) for both dose strengths with increasing the MIFs and Vins. The high proportion of EFPDs would improve the deposition in the peripheral airways in the lungs, and this is considered beneficial for the management of COPD (33,34). Our study showed that both the MIFs and Vins are important in maximising the EFPD of indacaterol (Fig.…”

Powder Particles and Technologies for Medicine Delivery to the Respiratory System: Challenges and Opportunities

“…This problem tries to find a possibly precise link between the particle size of inhaled drugs and the expected health benefit and must, in fact, acknowledge the complexity of particle deposition discussed in section 2. Some researchers claim that the mass of extra-fine particles (1-3 μm) is more relevant to the real deposition and health effects (de Boer A.H. et al, 2015). However, as shown in Fig.…”