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In this paper we demonstrate that the use of multiple orifices can improve the fine particle fraction (FPF) of pressurised metered-dose inhaler solution formulations by up to 75% when compared to a single orifice with an equivalent cross sectional area ( p 0.05 ). While prior work has relied on metal actuator components, improvements in micro injection moulding and micro drilling now make it possible to mass produce novel orifice shapes to achieve similar FPF gains in plastic parts, with orifice diameters less than 0.2 mm. The ability to create internal features inside the actuator is also demonstrated. We show through in vitro high speed imaging that twin orifice sprays merge quickly and act as a single, modified plume. We also show for the first time that FPF and fine particle dose (FPD) are strongly correlated with the distance at which the plume velocity decays to half its initial value ( R 2 = 0.997 and 0.95 respectively). When plume velocity & FPF are increased, mouthpiece deposition decreases. This suggests that while smaller orifices produce more fine particles, higher sustained plume velocities also entrain more of the fine particles produced at the periphery of the spray due to increased shear. The effect occurs within the mouthpiece and is thus unlikely to alter the flow field in the upper airway.

Inhalation drug delivery has seen a swift rise in the use of dry powder inhalers (DPIs) to treat chronic respiratory conditions. However, universal adoption of DPIs has been restrained due to their low efficiencies and significant drug losses in the mouth-throat region. Aerosol efficiency of DPIs is closely related to the fluid-dynamics characteristics of the inhalation flow generated from the devices, which in turn are influenced by the device design. In-vitro and particle image velocimetry (PIV) have been used in this study to assess the aerosol performance of a model carrier formulation delivered by DPI devices and to investigate their flow characteristics. Four DPI device models, with modification to their tangential inlets and addition of a grid, have been explored. Similar aerosol performances were observed for all four device models, with FPF larger than 50%, indicating desirable lung deposition. A high swirling and recirculating jet-flow emerging from the mouthpiece of the DPI models without the grid was observed, which contributed to particle deposition in the throat. DPI models where the grid was present showed a straightened outflow without undesired lateral spreading, that reduced particle deposition in the throat and mass retention in the device. These findings demonstrate that PIV measurements strengthen in-vitro evaluation and can be jointly used to develop high-performance DPIs.

This study presents the effect of a spiral mouthpiece design in a carrier-based dry powder inhalation on particle aerosol characteristics. Two kinds of mouthpieces, with spiral and non-spiral shaped flow channels, were fabricated by 3D-printing; particle image velocimetry and Anderson cascade impactor were performed to evaluate the drug aerosol characteristics. The obtained experimental results were in agreement with the simulation results of the computational fluid dynamics analysis. The spiral channel created a strong swirl motion of the air flow emitted from the mouthpiece exit, which produced angular momentum rather than the axial flow velocity in the forward direction. This is beneficial in terms of liberating the micronized drug particles from the carrier surface, and leads to more effective delivery of these drug particles to the peripheral target regions of the respiratory system. The spiral device could produce drug particles with significantly smaller mass median aerodynamic diameters and higher fine particle fraction than the non-spiral device.

Background In an effort to identify factors producing a finest mist from Jet-Nebulizers we designed 2 mouthpieces with 4 different internal designs and 1–3 compartments. Materials and methods Ten different drugs previous used with their “ideal” combination of jet-nebulizer, residual-cup and loading were used. For each drug the mass median aerodynamic diameter size had been established along with their “ideal” combination. Results For both mouthpiece, drug was the most important factor due the high F -values ( F large = 251.7, p F small = 60.1, p F large = 5.99, p = 0.001, F small = 1.72, p = 0.178). Cross designs create the smallest droplets (2.271) so differing from the other designs whose mean droplets were greater and equal ranging between 2.39 and 2.447. The number of compartments in the two devices regarding the 10 drugs was found not statistically significant ( p -values 0.768 and 0.532 respectively). Interaction effects between drugs and design were statistically significant for both devices ( F large = 8.87, p F small = 5.33, p Conclusion Based on our experiment we conclude that further improvement of the drugs intended for aerosol production is needed. In addition, the mouthpiece design and size play an important role in further enhancing the fine mist production and therefore further experimentation is needed.

Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different sites within the lungs. In this study, phase Doppler anemometry (PDA) was used to investigate the instantaneous droplet velocity emitted from MDIs as well as the corresponding droplet size distribution. The nine commercial MDI products surveyed showed significantly different droplet velocities, indicating that droplet velocity could be used as a discriminating parameter for in vitro testing of MDI products. The droplet velocity for all tested MDI products decreased when the testing distance was increased from 3 cm to 6 cm from the front of mouthpiece, with CFC formulations showing a larger decrease than HFA formulations. The mean droplet diameters of the nine MDIs were also significantly different from one-another. Droplet size measurements made using PDA (a number-based technique) could not be directly compared to results obtained using laser light scattering measurements (a volume-based technique). This work demonstrates that PDA can provide unique information useful for characterizing MDI aerosol plumes and evaluating MDI drug delivery efficiency. PDA could also aid the evaluation of in vitro equivalence in support of formulation or manufacturing changes and in evaluation of abbreviated new drug applications (ANDAs) for MDIs.

An inhaler design methodology was developed and then used to design a new dry powder inhaler (DPI) which aimed to fulfill two main performance requirements. The first requirement was that the patient should be able to completely empty the dry powder from the blister in which it is stored by inspiratory effort alone. The second requirement was that the flow resistance of the inhaler should be geared to optimum patient comfort. The emptying of a blister is a two-phase flow problem, whilst the adjustment of the flow resistance is an aerodynamic design problem. The core of the method comprised visualization of fluid and particle flow in upscaled prototypes operated in water. The prototypes and particles were upscaled so that dynamic similarity conditions were approximated as closely as possible. The initial step in the design method was to characterize different blister prototypes by measurements of their flow resistance and particle emptying performance. The blisters were then compared with regard to their aerodynamic performance and their ease of production. Following selection of candidate blisters, the other components such as needle, bypass and mouthpiece were dimensioned on the basis of node-loop operations and validation experiments. The final shape of the inhaler was achieved by experimental iteration.

Deposition of 99m Tc-labelled particles of disodium cromoglycate in the human respiratory tract after inhalation either from the conventional metered dose aerosol or from the new Ingelheim powder inhaler (FO II) was compared. Fractional deposition in the whole lung area, in the upper airways and in the device was measured using a gamma camera. Eight healthy informed volunteers participated in the inhalation test. The lung deposition of the inhaled drug was about 9% using the conventional aerosol actuator with the short plastic mouthpiece whereas, using the Ingelheim powder inhaler, on average 20% deposition in the whole lung area was achieved. In addition, with the Ingelheim inhaler drug particles seemed to be deposited in the more peripheral parts of the respiratory tract. The upper airway deposition was also reduced with the Ingelheim powder inhaler. On the other hand, a larger fraction of the drug dose was retained in the Ingelheim inhaler than in the aerosol actuator.