WO2016193743A1 - Aerosol delivery device - Google Patents

Abstract

An electrohydrodynamic aerosol delivery device (100) for delivering an aerosol to a user via inhalation, wherein the device is configured to vary one or more parameters which affect the particle size of the produced aerosol during a discrete inhalation event.

Description

AEROSOL DELIVERY DEVICE

FIELD OF THE INVENTION

The present invention relates to an aerosol delivery device for delivering an aerosol to a user which is more acceptable from a physiological and sensorial standpoint. BACKGROUND

Electronic cigarettes (e-cigarettes) and other similar devices have been used to produce a nicotine containing aerosol without the need to burn tobacco. However, providing an aerosol which is both physiologically and sensorially acceptable to consumers has been a challenge for many e-cigarette devices publically available. For example, on the one hand the consumer may be satisfied with the olfactory experience provided by the aerosol; however, they may perceive the physiological experience to be unsatisfactory.

The present invention is aimed at providing an aerosol delivery device which is capable of providing an aerosol which is acceptable from both a sensorial and physiological standpoint.

SUMMARY OF THE INVENTION In a first aspect of the present invention there is provided an electrohydrodynamic aerosol delivery device for delivering an aerosol to a user via inhalation, wherein the device is configured to vary one or more parameters which affect the particle size of the produced aerosol during a discrete inhalation event. By varying one or more of the parameters which affect the particle size of the produced aerosol during a discrete inhalation event it is possible to deliver an aerosol with a bimodal particle size distribution to the user during the same discrete inhalation event. By providing an aerosol with a bimodal particle size distribution, it is possible to provide an aerosol that is acceptable from both a sensorial and physiological standpoint. More specifically, it is understood that particles which have a median mass aerodynamic diameter (MMAD) of less than 10 μιτι are able to bypass the buccal cavity and deposit in the lung, with sizes less than 5 μιη able to enter the deep lung. However, whilst this may produce an acceptable physiological effect on the user, the sensorial qualities of the aerosol may be compromised since the user is less able to perceive the presence of the aerosol in the buccal cavity. Conversely, particles which have a median mass aerodynamic diameter (MMAD) of greater than 5 μιη are generally more susceptible to deposition in the buccal cavity and as a result are more perceptible to a user from a sensorial (olfactory) perspective. When it is desired that the aerosol provides sensorial characteristics, as well as physiological characteristics, to the user, it is a particular advantage to be able to deliver an aerosol which has a particle size distribution tailored to these requirements, e.g. one which contains an effective amount of smaller particles which can have a physiological impact and an effective amount of larger particles which can have a sensorial impact .

Electrohydrodynamic atomizers have previously been suggested in the art for the pulmonary delivery of pharmaceutical formulations, but these have focussed on the provision of aerosols with well defined, narrow particle size distributions for every inhalation. In complete contrast, the present invention is able to provide an aerosol with varied particle size distributions.

The electrohydrodynamic aerosol delivery device may comprise

a power source;

a liquid delivery mechanism;

a nozzle; and

a control unit.

The nozzle may comprise an outlet orifice and a ground electrode, the outlet orifice and ground electrode being spaced apart from one another. The nozzle may comprise multiple outlet orifices. The power source may be electrically connected to the nozzle such that when activated an electrical potential is applied across the outlet orifice and the ground electrode.

The power source may be activated in response to an input from a user. The input from the user can be direct activation and/or indirect activation.

The direct activation may require the user to interact directly with the device.

The power source may be activated in response to the user inhaling through the device or actuating a button on the device.

The power source may trigger commencement of the inhalation event. The one or more parameters which affect the particle size of the produced aerosol may be varied within 3 seconds of the commencement of the inhalation event.

The one or more parameters which affect the particle size of the produced aerosol may be varied within 2 seconds of the commencement of the inhalation event.

The one or more parameters which affect the particle size of the produced aerosol may be varied within 1 second of the commencement of the inhalation event. The one or more parameters which are varied during the inhalation event may be selected from: flow of liquid to the nozzle; and

the potential difference applied between the ground electrode and the orifice of the nozzle. The flow of liquid to the nozzle may be controlled through the liquid delivery mechanism.

The liquid delivery mechanism may be powered or non-powered.

The liquid delivery mechanism may be configured to deliver flow rates in the range of 0.01 to 10 ml/h.

The one or more parameters which may be varied during the inhalation event is flow of liquid to the nozzle.

The liquid delivery mechanism may be configured to deliver different flow rates during an inhalation event.

The liquid delivery mechanism may be configured to deliver flow rate (Ql) and flow rate (Q2) during an inhalation event, wherein (Ql) and (Q2) are different. The flow rate (Ql) may be smaller than flow rate (Q2).

The flow rate (Ql) may precede flow rate (Q2). The flow rate (Q2) may precede flow rate (Ql).

The flow rate (Ql) may be in the range of 0.01 to 1 ml/h, preferably 0.01 to 0.1 ml/h. The flow rate (Q2) may be in the range of 0.5 to 10 ml/h, preferably 1.0 to 1.2 ml/h.

The control unit may be configured to increase or decrease the flow of liquid to the nozzle during an inhalation event.

The potential difference applied between the orifice and the ground electrode may be substantially constant for the inhalation event. The one or more parameters which are varied during the inhalation event may be potential difference applied between the orifice and the ground electrode.

The control unit may be configured to control the power source to vary the potential difference applied between the orifice and the ground electrode during an inhalation event.

The variation of the potential difference applied between the orifice and the ground electrode may be increased, decreased or pulsed during an inhalation event.

The potential difference applied between the orifice and the ground electrode may be pulsed during an inhalation event.

The pulsed potential difference may be delivered at a frequency linked to one or more of:

one or more airflow characteristics through the device as a result of user inhalation; and the flow rate of liquid to the nozzle.

The parameters which are varied during the inhalation event may be potential difference applied between the orifice and the ground electrode and flow of liquid to the nozzle.

The control unit may measure one or more airflow characteristics through the device as a result of user inhalation and in response thereto modifies one or more of:

potential difference applied between the orifice and the ground electrode; and

flow of liquid to the nozzle. The variation of the one or more of the parameters which are to be varied may lead to an aerosol having a particle size distribution with a maxima at less than 5 microns and a maxima at greater than 5 microns. The variation of the one or more of the parameters which are to be varied may lead to an aerosol having a particle size distribution with a maxima at less than 3 microns and a maxima at greater than 8 microns.

The electrohydrodynamic aerosol delivery device may further comprise a liquid store in fluid communication with the liquid delivery mechanism.

The liquid store may be replaceable or re-fillable.

The electrohydrodynamic aerosol delivery device may further comprise a mouthpiece arranged over the nozzle. The mouthpiece has an air channel which communicates the orifice of the nozzle with the buccal cavity of the user.

Bimodal distribution Reference in the present disclosure is made to an aerosol with a bimodal particle size distribution. This is generally well understood in the art as referring to an aerosol wherein the particle size distribution contains two different modes. These appear as distinct peaks (local maxima) in the particle size distribution for the aerosol. In one embodiment, the aerosol is one where the particle size distribution has one peak equal to or below 5 μιη, and a second peak greater than 5 μιη, preferably greater than 7 μιτι preferably greater than 10 μηι. In one embodiment, the aerosol is one where the particle size distribution has one peak falling in the range of about 0.1 to 5 μιη, and a second peak falling in the range of about 10 to 100 pm.

Inhalation event

Reference in the present disclosure is made to an inhalation event. An inhalation event refers to a discrete period of inhalation wherein the air flow through the device increases from zero to a maximum and then reduces back to zero. There may be one or more flow maxima occurring throughout the inhalation event, with the proviso that the inhalation event is deemed to have finished when the flow through the device has dropped to substantially zero. In this context, it will be understood that there are numerous ways in which flow through a device can be measured, such as via pressure change, rate of airflow etc. The present disclosure is not limited to an inhalation being determined in one particular manner.

The inhalation event will typically last for a number of seconds, for example for around 3 seconds. In one embodiment, an inhalation event has a duration of up to 1 second. In one embodiment, an inhalation event has a duration of up to 2 seconds. In one embodiment, an inhalation event has a duration of up to 3 seconds. In one embodiment, an inhalation event has a duration of up to 4 seconds. In one embodiment, an inhalation event has a duration of up to 5 seconds. In one embodiment, an inhalation event has a duration of 1 second or more, 2 seconds or more, 3 seconds or more, 4 seconds or more, 5 seconds or more.

During an inhalation event, the aerosol delivery device is activated for all or part of the inhalation event. In this regard, activation refers to the application of an electrical potential across a nozzle of the device which expels the formulation into an aerosol, and a ground electrode spaced apart from the nozzle. As will be explained in more detail below, the electrical potential applied can either be constant for the duration of the inhalation event, or can vary. Other aspects of the device may also be activated during an inhalation event. For example, where the device comprises a liquid delivery mechanism, it may be that this is supplied with power in order to drive liquid towards the nozzle. However, the liquid delivery mechanism need not require power, as it may rely on physical forces to deliver liquid to the nozzle, for example via capillary action or gravity.

Electrohydrodynamic aerosol generation

Electrohydrodynamics involves the study of the dynamics of electrically charged fluids. In the context of aerosol generation, electrohydrodynamics can refer to the generation of an aerosol as a result of imparting an electrically conductive liquid with electrical charge. As the electrical charge increases within the liquid, repulsive forces drive the liquid apart to form a jet which breaks into droplets. The ability of the liquid to form droplets depends on a number of factors, including the surface tension of the liquid, its electrical properties, the magnitude of the electric field and the flow rate of the liquid to the nozzle at which the electric field is applied. In this regard, the parameters affecting droplet formation have been studied extensively and it has been described that the surface tension of the liquid generally balances against the repulsive effects of the charge build up so as to form a cone (a Taylor cone) of droplets which extend from the nozzle of the device

("Electrohydrodynamics Spraying Functioning Modes: A Critical Review", Cloupeau et al, J. Aerosol Sci., Vol. 25, No. 6, 1994). At the tip of the Taylor cone, the repulsive forces generally overcome the surface tension and a jet of liquid droplets is expelled. It is generally understood that the particle size of these droplets is generally uniform, at least to the extent that the aerosols produced can generally be classed as having a unimodal particle size distribution. In this regard, it is generally known in the art how the particle size of an electrohydrodynamic aerosol can be influenced. Reference is made to Yurteri et al, "Producing Pharmaceutical Particles via Electrospraying with an Emphasis on Nano and Nano Structured Particles -A review", Kona Powder and Particle Journal No. 28 (2010), 91-115, which describes the relevant factors affecting the particle size of aerosols produced in the "cone jet mode".

As described above, in a first aspect there is provided an electrohydrodynamic aerosol delivery device for delivering an aerosol to a user via inhalation, wherein the device is configured to vary one or more parameters which affect the particle size of the produced aerosol during a discrete inhalation event.

The particle size distribution of the produced aerosol may be affected by a number of parameters, including the rate of delivery of liquid to the nozzle, the size of the electric field applied between the nozzle aperture and ground electrode (effectively the current applied by the power source), the surface tension of the formulation to be aerosolized, the electrical properties of the formulation to be aerosolized, the type of nozzle and the distance between the nozzle and the ground electrode.

Whilst it is envisaged that any one of the above parameters could be varied during an inhalation event, in one embodiment the one or more parameters that are varied during an inhalation event are selected from:

· flow rate to the nozzle; and/or

• potential difference applied between the orifice and the ground electrode.

It is generally understood that the formation of a Taylor cone is important for the generation of an electrohydrodynamic aerosol. However, as described in to Yurteri et al, "Producing Pharmaceutical Particles via Electrospraying with an Emphasis on Nano and Nano Structured Particles - A review", Kona Powder and Particle Journal No. 28 (2010), 91-115, other jet modes are possible, including the intermittent cone jet mode, the multi-jet mode and the rim emission mode. For example, a cone jet from an ethanol liquid can be provided under conditions of constant flow and potential for a Gauge 22 Nozzle (Nordson EFD) with an inner/outer diameter of 0.41/0.72 mm; a potential of + 3.3 kV applied across the nozzle and a ground electrode at a distance of 3cm, with a liquid flow rate of 1 mL/h (Yurteri et al, Kona Powder and Particle Journal No. 28 (2010), 91-115, Fig. 1).

For devices operating in a cone jet mode, the produced jet can be characterised into two further sub-categories: the varicose mode and the whipping jet mode. The applied electric potential is the primary factor affecting the sub-operating mode (see Yurteri et al, Kona Powder and Particle Journal No. 28 (2010), 91-115, Fig. 6 a) and b)).

The particle size of the produced aerosol can be predicted using well-established scaling laws. In particular, for a given liquid formulation, the particle size of the produced aerosol can be predicted according to the following formulae: cone jet (varicose mode) d,varicose

where:

d d varicose ~^tne diameter of the droplet based on varicose break-up mechanism [m]

P = density of the liquid to be aerosolized [kgirf³]

£Q = electric permittivity of a vacuum [C²N ^m^"2]

Y = liquid surface tension [Nrrf¹]

K - liquid conductivity [Srrf ] 1

cone jet (whipping mode) - d d.whipping

where:

d d,whipping meter of the droplet based on whipping break-up mechanism

£Q = electric permittivity of a vacuum [C²N^_1m^"2]

Q = liquid flow rate to the nozzle [mV¹]

y = liquid surface tension [Nnrf¹] electric current [Cs^"1] It will be understood that for a particular liquid under constant temperature and pressure, the values for γ (liquid surface tension), p (density) and K (liquid conductivity) will generally be constant. As a result, the particle size of the aerosol produced can be affected by modifying Q, the liquid flow rate and (V), the potential applied between the ground electrode and the orifice of the nozzle (since the electric current / effectively incorporates the potential difference applied between the orifice and the ground electrode). In this regard, it will be understood that for any new liquid being aerosolized, calibration of the parameters will be required such that a stable Taylor cone is produced. Using these parameters as a "default" for that particular liquid, the device parameters can be modified so as to affect particle size as may be desired by the user. Flow rate (Q)

In one embodiment, the aerosol delivery device comprises a liquid delivery mechanism configured to deliver liquid to the nozzle. Where the nozzle contains multiple orifices, the flow rate described herein may be per orifice. The liquid delivery mechanism may be powered, in which case it may be driven for example via a pump. Alternatively, the liquid delivery mechanism may be non-powered, in which case it may be driven by capillary action.

In one embodiment, the liquid delivery mechanism is configured to deliver liquid to the nozzle at a constant rate for a single inhalation event. In this embodiment, the flow rate (¾) of liquid to the nozzle is typically in the range 0.01 to 10 ml/h, preferably 0.05 to 10 ml/h, preferably 0.1 to 10 ml/h, preferably 0.15 to 10 ml/h, preferably 0.2 to 10 ml/h, preferably 0.5 to 10 ml/h, preferably 1.0 to 10 ml/h, preferably 1.5 to 10 ml/h, 2 to 9 ml/h, preferably 3 to 8 ml/h, preferably 4 to 7 ml/h, preferably 5 to 6 ml/h. The flow rate need not be the same for all inhalation events. In particular, the liquid delivery mechanism may be controlled such that the flow rate can be varied between inhalation events. This has the advantage that the particle size distribution of the produced aerosol can be shifted up or down in mean size depending on the flow rate set by the user. In one embodiment, the liquid delivery mechanism may be controlled by a control unit (such as a control microchip) which modulates the flow rate. In this embodiment, the liquid delivery mechanism may comprise a pump, such as a micro pump, and the control unit is able to control the pump to increase or decrease the flow rate.

In this regard, the flow rate (Q_c) may be set at a default value, such as 1 ml/hr. The control unit can then be configured to increase or decrease the flow rate between inhalation events relative to this default flow rate.

In one embodiment, the liquid delivery mechanism is configured to deliver the formulation to the nozzle at a varying flow rate during an inhalation event. Thus, whilst the flow rate to the nozzle may vary from inhalation event to inhalation event (as described above) the present embodiment envisages that the flow rate during a single inhalation event may vary. As described above, the flow rate (in this case Q_v) has a direct influence on the particle size of the aerosol produced by the device. Therefore, by varying the flow rate during a single inhalation event, the particle size distribution of the aerosol can be modified from unimodal to bimodal.

Where the liquid delivery mechanism is configured to deliver the liquid to the nozzle at a varying flow rate for a single inhalation event, the flow rate (Q_v) is typically varied such that when the surface tension and electrical properties of the liquid are constant, and the size of the electric field is constant, an aerosol is produced with a bimodal particle size distribution.

In one embodiment, the flow rate (Q) to the nozzle can be, or is, increased as the inhalation event progresses. In one embodiment, the flow rate (Q) to the nozzle can be, or is, decreased as the inhalation event progresses. In this regard, the increase or decrease is generally relative to the flow rate at the beginning of an inhalation event. In one embodiment, the liquid delivery mechanism is configured to deliver the liquid to the nozzle at two or more different flow rates for a single inhalation event. In one embodiment, the liquid delivery mechanism is configured to deliver the liquid to the nozzle at two different flow rates (Ql and Q2) for a single inhalation event.

In one embodiment, flow rate (Ql) is smaller than flow rate (Q2). In one embodiment, flow rate (Ql) is typically in the range 0.01 to 1 ml/h, preferably 0.01 to 0.9 ml/h, preferably 0.01 to 0.8 ml/h, preferably 0.01 to 0.7 ml/h, preferably 0.01 to 0.6 ml/h, preferably 0.01 to 0.5 ml/h, preferably 0.01 to 0.4 ml/h, preferably 0.01 to 0.3 ml/h, preferably 0.01 to 0.2 ml/h, preferably 0.01 to 0.1 ml/h.

In one embodiment, flow rate (Ql) is typically in the range 0.02 to 0.1 ml/h, preferably 0.03 to 0.1 ml/h, preferably 0.04 to 0.1 ml/h, preferably 0.05 to 0.1 ml/h.

In one embodiment , flow rate (Ql) is typically in the range 0.05 to 0.09 ml/h, preferably 0.05 to 0.08 ml/h, preferably 0.05 to 0.07 ml/h, preferably 0.05 to 0.06 ml/h.

In one embodiment, flow rate (Ql) is 0.6 ml/h or less, preferably 0.5 ml/h or less, preferably 0.4 ml/h or less, preferably 0.3 ml/h or less.

In one embodiment, flow rate (Q2) is typically in the range 0.5 to 10 ml/h, preferably 0.6 to 10 ml/h, preferably 0.7 to 10 ml/h, preferably 0.8 to 10 ml/h, preferably 0.9 to 10 ml/h. In one embodiment, flow rate (Q2) is typically in the range 1 to 10 ml/h, preferably 1.1 to 10 ml/h, preferably 1.2 to 10 ml/h, preferably 1.3 to 10 ml/h, preferably 1.4 to 10 ml/h, preferably 1.5 to 10 ml/h, preferably 2 to 10 ml/h, preferably 3 to 10 ml/h, preferably 4 to 10 ml/h, preferably 5 to 10 ml/h. In one embodiment, flow rate (Q2) is typically in the range 1 to 5 ml/h, preferably 1 to 4 ml/h, preferably 1 to 3 ml/h, preferably 1 to 2 ml/h. In one embodiment, flow rate (Q2) is 0.5 ml/h or more, preferably 0.6 ml/h or more, preferably 0.7 ml/h or more, preferably 0.8 ml/h or more, preferably 0.9 ml/h or more, preferably 1.0 ml/h or more, preferably 1.2 ml/h or more, preferably 1.3 ml/h or more. Flow rates (Ql) and (Q2) may occur in any order during an inhalation event. In one embodiment, flow rate (Ql) precedes flow rate (Q2). In one embodiment, flow rate (Q2) precedes flow rate (Ql).

Respective flow rates Ql and Q2 may be provided for varying amounts of time during a single inhalation event. In one embodiment, the flow rate profile in terms of the percentage of the event for which a particular flow rate is in operation for a single inhalation event may be according to the following ratios of Ql to Q2: 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, 95:5.

It will also be understood that the flow rate (Q) could be configured to vary according to the inhalation profile. For example, where an inhalation has a varying profile in terms of airflow, the control unit may detect this and control the liquid delivery mechanism to modulate the flow rate in response to the inhalation profile. In one embodiment, a particular flow rate (Ql) or (Q2), or both, may be increased, or decreased in response to an inhalation that increases or decreases in terms of any one of airflow, pressure drop or any other suitable means for measuring the airflow

characteristics through an aerosol delivery device. In this regard, the device can be provided with a sensor, such as a digital pressure sensor, which monitors the pressure within the device during an inhalation even. The control unit is configured to receive the output of the sensor and to correspondingly control the flow rate (Ql), (Q2) or both, in response to changes in the sensor output.

The control unit can be configured to receive a manual instruction to increase the flow rate via a button, dial or the like which is present on the device. Alternatively, the control unit could be configured to receive instructions from a remote device, such as a smart phone or computer, via a wireless connection (Bluetooth Low Energy or the like) or a wired connection.

Potential (V)

As will be apparent from the above, the potential applied across the orifice and the ground electrode impacts the particle size of the droplets produced. Briefly, this is because depending on the electrical potential applied across the orifice and the ground electrode, the charge distribution throughout the liquid will be affected and thus the extent of the repulsive forces experienced within the liquid will vary. Accordingly, in one embodiment, the potential applied across the orifice and the ground electrode is varied during the inhalation event. This variation could be an increase, decrease or pulse, depending on the desired profile of the particle size required.

In one embodiment, the potential is varied during the inhalation event. In this embodiment, the control unit is configured to control the power source such that potential (VI) and potential (V2) are applied across the ground electrode and orifice during an inhalation event. In one embodiment, potential (VI) is smaller than potential (V2). In one embodiment, potential (VI) is delivered in advance of potential (V2). In one embodiment, potential (V2) is delivered in advance of potential (V2).

In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±lkV to +10kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±2kV to ±10kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±3kV to +10kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±4kV to ±10kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range +5kV to ±10kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±lkV to ±9kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range +lkV to ±8kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range ±lkV to ±7kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range +lkV to +6kV. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is in the range +lkV to ±5kV.

As mentioned above, in one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle may be kept constant during an inhalation event (provided one other parameter as mentioned above is varied). In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is varied during an inhalation event such that at least two potentials are applied during an inhalation event. It may also be that more than two different potentials are applied during the inhalation event. In one embodiment, the potential difference applied between the ground electrode and the orifice of the nozzle is dynamically varied.

In one embodiment, potential (VI) is in the range of from +lkV to +5kV. In one embodiment, potential (VI) is in the range of from +1.5kV to +5kV. In one embodiment, potential (VI) is in the range of from+ 2kV to +5kV. In one embodiment, potential (VI) is in the range of from +2.5kV to

+5kV. In one embodiment, potential (VI) is in the range of from +3kV to +5kV. In one embodiment, potential (VI) is in the range of from +3.5kV to +5kV. In one embodiment, potential (VI) is in the range of from +4kV to +5kV. In one embodiment, potential (VI) is in the range of from +4.5kV to +5kV.

In one embodiment, potential (VI) is in the range of from -lkV to -5kV. In one embodiment, potential (VI) is in the range of from -1.5kV to -5kV. In one embodiment, potential (VI) is in the range of from -2kV to -5kV. In one embodiment, potential (VI) is in the range of from -2.5kV to -5kV. In one embodiment, potential (VI) is in the range of from -3kV to -5kV. In one embodiment, potential (VI) is in the range of from -3.5kV to -5kV. In one embodiment, potential (VI) is in the range of from -4kV to -5kV. In one embodiment, potential (VI) is in the range of from -4.5kV to - 5kV.

In one embodiment, potential (V2) is in the range of from above +5kV to +10kV. In one

embodiment, potential (V2) is in the range of from +5.5kV to +10kV. In one embodiment, potential (V2) is in the range of from +6kV to +10kV. In one embodiment, potential (V2) is in the range of from +6.5kV to +10kV. In one embodiment, potential (V2) is in the range of from +7kV to +10kV. In one embodiment, potential (V2) is in the range of from +7.5kV to +10kV. In one embodiment, potential (V2) is in the range of from +8kV to +10kV. In one embodiment, potential (V2) is in the range of from +8.5kV to +10kV. In one embodiment, potential (V2) is in the range of from +9kV to +10kV.

In one embodiment, potential (V2) is in the range of from above -5kV to -lOkV. In one embodiment, potential (V2) is in the range of from -5.5kV to -lOkV. In one embodiment, potential (V2) is in the range of from -6kV to -lOkV. In one embodiment, potential (V2) is in the range of from -6.5kV to - lOkV. In one embodiment, potential (V2) is in the range of from -7kV to -lOkV. In one embodiment, potential (V2) is in the range of from -7.5kV to -lOkV. In one embodiment, potential (V2) is in the range of from -8kV to -lOkV. In one embodiment, potential (V2) is in the range of from -8.5kV to - lOkV. In one embodiment, potential (V2) is in the range of from -9kV to -lOkV

It will also be understood that the potential (V) could be configured to vary according to the inhalation profile. For example, where an inhalation has a varying profile in terms of airflow, the control unit may detect this and control the power source to modulate the potential (VI) in response to the inhalation profile. In one embodiment, a particular voltage (VI) or (V2), or both, may be increased, or decreased in response to an inhalation that increases or decreases in terms of any one of airflow, pressure drop or any other suitable means for measuring the airflow

characteristics through an aerosol delivery device. In this regard, the device can be provided with a sensor, such as a digital pressure sensor, which monitors the pressure within the device during an inhalation even. The control unit is configured to receive the output of the sensor and to correspondingly control the potential (VI), (V2) or both, in response to changes in the sensor output. The control unit can be configured to receive a manual instruction to increase the flow rate via a button, dial or the like which is present on the device. Alternatively, the control unit could be configured to receive instructions from a remote device, such as a smart phone or computer, via a wireless connection (Bluetooth Low Energy or the like) or a wired connection. Other aspects

In one embodiment, the aerosol delivery device of the present invention comprises one nozzle. In this embodiment, the aerosol delivery device is typically configured to deliver a single type of liquid to the nozzle. In an alternative embodiment, the aerosol delivery device may have a single nozzle, but be configured to deliver different liquids to the nozzle. In one embodiment the different liquids are delivered sequentially to the nozzle.

Suitable liquids for EH DA In one embodiment, the aerosol delivery device is configured to deliver a liquid to the nozzle. In this embodiment, the liquid may have a surface tension in the range of from about 15 to about 80 mN/m, preferably from about 20 to about 75 mN/m, preferably from about 25 to about 70 mN/m, preferably from about 40 to about 70 mN/m. In one embodiment, the conductivity of the liquid is greater than about 0.005 S/m, preferably more than about 0.003 S/m, preferably more than about 0.0025 S/m, preferably more than about 0.002 S/m, preferably more than about 0.0016 S/m, preferably more than about 0.002 S/m, preferably more than about 0.0001 S/m. In one

embodiment, the liquid has conductivity in the range of 0.02 to 0.0001 S/m. In one embodiment, the liquid to be aerosolised comprises nicotine. In one embodiment, the liquid to be aerosolised comprises water. In one embodiment, the liquid to be aerosolised contains glycerol. In one embodiment, the liquid to be aerosolised comprises water, nicotine and glycerol. In one embodiment, the liquid to be aerosolised comprises water and glycerol. The liquid may also comprise other components such as flavourants etc.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 - Provides a schematic representation of a device 100 according to the present invention. DETAILED DESCRIPTION

The electrohydrodynamic aerosol delivery device of the present invention will now be described in more detail with reference to the non-limiting embodiments shown in the Figure.

Figure 1 shows electrohydrodynamic aerosol delivery device 100 comprising a housing 110, a power source 120, a liquid store 130, a liquid delivery mechanism 140, a nozzle 150, a control unit 170, and an (optional) manual input device 170.

Housing 110 can take any form, however it is generally intended to be sized so as to hold the above mentioned internal components, yet be suitable to be held in the hand of a user. The housing may have a rectangular, circular, oval, droplet or polygonal cross-section. Typically, housing 100 comprises the power source 120. Power source 120 may be replaceable or rechargeable (e.g.

though a suitable recharge connection such as a USB (standard, mini or micro) port. Typical power sources are rechargeable batteries, such as Lithium-ion batteries. Housing 110 also comprises liquid store 130 which is designed to hold a portion of liquid to be aerosolized at the nozzle 150. The liquid store may be replaceable or refillable. The liquid store 130 is in fluid communication with the liquid delivery mechanism 140. The liquid delivery mechanism 140 may be powered or non-powered - that is to say, the liquid may be delivered to the nozzle 150 via some form of powered mechanism, e.g. a micro pump, or it may be that the liquid is delivered to the nozzle 150 under physical influence, e.g. via capillary action. Thus, where the liquid delivery mechanism 140 is non-powered, it may take the form of a capillary tube. Alternatively, it may be possible for the user to squeeze the housing 110 such that it deforms and in turn deforms the liquid store so as to drive liquid along the liquid delivery mechanism 140. Where the liquid delivery mechanism is powered, it typically comprises a pump 141 (not shown). Pump 141 is controlled by control unit 160 and powered by power source 120. When the power source is activated (as will be explained further below), power is delivered to pump 141 and liquid is forced from the liquid store 130 to the nozzle at a flow rate (Q,), as described above. Further, as described above, the flow rate can be varied during an inhalation event. Nozzle 150 is attached to housing 110 and comprises an outlet orifice 151 (not shown) and a ground electrode 152 (not shown). When the device is actuated, power source 120 is activated to deliver current to pump 141 (if present) and also to establish a potential difference between the outlet orifice 151 and the ground electrode 152. Liquid present at the orifice 151 will then become charged. The charged liquid will then begin to form a cone (a Taylor cone) due to the internal repulsive forces and the countering surface tension forces of the liquid. Once the charge in the liquid reaches a level at which the repulsive forces within the liquid overcome the surface tension of the liquid, the liquid will begin to break up and form droplets with a particular particle size. The charged ions within the liquid will be repelled along axis of the cone, colliding with liquid molecules and ejecting them as a jet.

The activation of the device 100 will now be described in further detail. In use, the user will place the nozzle of the device (optionally shielded with a mouthpiece with an air channel) in their mouth and inhale. Upon inhalation, the device will be actuated as a result of a pressure sensor (or other suitable sensor) detecting the inhalation. Alternatively, the device may be manually activated by the user by actuating a button 170 present on the device at substantially the same time as inhaling.

Where a button is used, the device may remain actuated as long as the button is actuated, or it may remain actuated for a defined period of time following the initial actuation and release of the button (such as for 1, 2, 3 or 5 seconds). Control unit 160 is configured to receive an input from the input device (be it sensor, button or both) and to correspondingly activate the power source 120. Power is then delivered to the liquid delivery mechanism (if a pump is present) and an electrical potential is applied across the orifice 151 and the ground electrode 152 of the nozzle 150. At this point of actuation, control unit 160 also logs the start of an inhalation event. Depending on how the control unit has been configured by the user (or how it is initially configured as a default setting), one or more of the parameters that affects the particle size of the produced aerosol will be varied during the inhalation event. The impact of varying one or more of these parameters is that, for a single inhalation event, the particle size distribution of the aerosol produced will have two maxima, i.e. it will approximate a bimodal particle size distribution. This variation of parameters has been explained above and could involve varying the flow of liquid to the nozzle, the potential difference applied between the orifice and the nozzle, or both. As a result, the inhalation event will proceed to its conclusion and an aerosol having a particle size distribution approximating a bimodal particle size distribution will have been delivered to the user. This is highly advantageous as an aerosol can be delivered which is acceptable from both a physiological and sensorial standpoint.

Once the inhalation event has ended (logged by the control unit due to either an indication from the sensor that inhalation is no longer occurring, the button has been released, or the relevant time has elapsed), power will no longer be supplied to the liquid delivery mechanism or the nozzle and aerosol production will cease.

As explained above, the present invention provides the advantages of delivering an aerosol which is acceptable from both a physiological and sensorial standpoint. Further, the present invention allows for a device where the particle size can be easily tuned since the parameters affecting particle size can be configured by the user. In this regard, not only can the particle size be tuned intra-inhalation (i.e. during an inhalation event), but the particle size can be tuned inter-inhalation (i.e. between inhalation events). In this regard, it may be that the device has various predetermined settings which deliver aerosols with defined particle sizes. For example, the control unit 160 may be preprogrammed with various modes (such as high, medium, and low) which have different particle size distributions. For example, a "high" mode may result in the device generating a particle size distribution with a greater frequency of particles sized at 5 microns or below (if in this context "high" refers to high physiological delivery). Conversely, a "high" mode may result in the device generating a particle size distribution with a greater frequency of particles sized at above 5 microns (if in this context "high" refers to high olfactory delivery).

Examples e ability to modify the particle size of the aerosol will now be referred to in the following non- miting examples. Example 1

A liquid comprising 25 % water and 75% glycerol was prepared (sample 1). A liquid comprising 50% water and 50% glycerol was prepared (sample 2). The surface tension, density, conductivity, dielectric constant and viscosity was determined for each sample as shown in Table 1 below.

Table 1

Taking the values in Table 1 and inserting them into respective formulas (1) and (2) gives the particle sizes listed in Table 2 for specific flow rates and currents.

1

d_d,varicose = (^^-)⁶ - (Equation 1)

d_d>whip≠ng = (o.8²⁸⁸^^yQ - (Equation 2)

Table 2

0.0133 3.694 19.6 0.776 1.73

0.015 4.167 20.8 0.824 1.80

0.0167 4.639 21.9 0.870 1.87

0.0184 5.111 23.0 0.913 1.93

0.0201 5.583 24.0 0.955 1.99

0.0218 6.056 25.0 0.995 2.04

0.0235 6.528 25.9 1.03 2.10

0.0252 7.000 26.8 1.07 2.15

0.0269 7.472 27.7 1.11 2.19

0.0286 7.944 28.5 1.14 2.24

0.0303 8.417 29.4 1.17 2.28

0.1 27.78 52.9 2.14 3.42

0.3 83.33 90.9 3.71 4.96

1 277.8 165 6.80 7.44

As can be seen from Table 2, the particle sizes of the aerosols derived from Sample 1 vary according to increasing flow rate, regardless of whether a varicose sub-mode or a whipping sub-mode is utilised. Accordingly, by varying the flow rate (Q) of the liquid during an inhalation event it is possible to prepare a single aerosol with a range of particle sizes. In essence, the user can tune the particle size of the device by varying the flow rate. However, it is particularly advantageous that the particle size can be varied across the threshold at which on the one hand particles are more likely to deposit in the deep lung (5 micron and below) and on the other hand particles are more likely to deposit in the buccal cavity (above 5 micron). In particular, it can be seen that when the device is operated in a varicose sub-operating mode, varying the flow rate above and below approximately 0.3 ml/hr will lead to an aerosol with particles below 5 microns and with particles above 5 microns.

Table 3 below shows a similar picture for sample 2 aerosols. Table 3

0.0201 5.583 13.7 1.16 2.85

0.0218 6.056 14.3 1.21 2.93

0.0235 6.528 14.8 1.26 3.01

0.0252 7.000 15.4 1.30 3.08

0.0269 7.472 15.9 1.34 3.15

0.0286 7.944 16.4 1.39 3.21

0.0303 8.417 16.8 1.43 3.28

0.1 27.78 30.3 2.60 4.91

0.3 83.33 52.1 4.52 7.11

1 277.8 94.3 8.27 10.7

As can be seen from Table 3, the particle sizes of the aerosols derived from Sample 2 vary according to increasing flow rate, regardless of whether a varicose sub-mode or a whipping sub-mode is utilised. Accordingly, by varying the flow rate (Q.) of the liquid during an inhalation event it is possible to prepare a single aerosol with a range of particle sizes. In essence, the user can tune the particle size of the device by varying the flow rate. However, it is particularly advantageous that the particle size can be varied across the threshold at which on the one hand particles are more likely to deposit in the deep lung (5 micron and below) and on the other hand particles are more likely to deposit in the buccal cavity (above 5 micron). In particular, it can be seen that when the device is operated in a varicose sub-operating mode, varying the flow rate above and below approximately 0.3 ml/hr will lead to an aerosol with particles below 5 microns and with particles above 5 microns (in fact as large as 8 microns).

The particle size range possible is even more pronounced when operating in the whipping sub- operating mode.

Various modifications of the present invention will be apparent to the person skilled in the art, and the present disclosure is not to be limited to the specific embodiments described herein.

Claims

1. An electrohydrodynamic aerosol delivery device for delivering an aerosol to a user via inhalation, wherein the device is configured to vary one or more parameters which affect the particle size of the produced aerosol during a discrete inhalation event.

2. The electrohydrodynamic aerosol delivery device according to claim 1, comprising:

a power source;

a liquid delivery mechanism;

a nozzle; and

a control unit.

3. The electrohydrodynamic aerosol delivery device according to claim 2, wherein the nozzle comprises an outlet orifice and a ground electrode, the outlet orifice and ground electrode being spaced apart from one another.

4. The electrohydrodynamic aerosol delivery device according to claim 2 or claim 3, wherein the power source is electrically connected to the nozzle such that when activated an electrical potential is applied across the outlet orifice and the ground electrode.

5. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 4, wherein the power source is activated in response to an input from a user.

6. The electrohydrodynamic aerosol delivery device according to claim 5, wherein the input from the user can be direct activation and/or indirect activation.

7. The electrohydrodynamic aerosol delivery device according to claim 6, wherein the direct activation requires the user to interact directly with the device.

8. The electrohydrodynamic aerosol delivery device according to claim 7, wherein the power source is activated in response to the user inhaling through the device or actuating a button on the device.

9. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 8, wherein activating the power source triggers commencement of the inhalation event.

10. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 9, wherein the one or more parameters which affect the particle size of the produced aerosol are varied within 3 seconds of the commencement of the inhalation event.

11. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 10, wherein the one or more parameters which affect the particle size of the produced aerosol are varied within 2 seconds of the commencement of the inhalation event.

12. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 11, wherein the one or more parameters which affect the particle size of the produced aerosol are varied within 1 second of the commencement of the inhalation event.

13. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 12, wherein the one or more parameters which are varied during the inhalation event are selected from: flow of liquid to the nozzle; and

potential difference applied between the orifice and the ground electrode.

14. The electrohydrodynamic aerosol delivery device according to claim 13, wherein the flow of liquid to the nozzle is controlled through the liquid delivery mechanism.

15. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 14, wherein the liquid delivery mechanism is powered or non-powered.

16. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 15, wherein the liquid delivery mechanism is configured to deliver a flow rates in the range of 0.01 to 10 ml/h.

17. The electrohydrodynamic aerosol delivery device according to any one of claims 13 to 16, wherein the one or more parameters which are varied during the inhalation event is flow of liquid to the nozzle.

18. The electrohydrodynamic aerosol delivery device according to claim 17, wherein the liquid delivery mechanism is configured to deliver different flow rates during an inhalation event.

19. The electrohydrodynamic aerosol delivery device according to claim 18, wherein the liquid delivery mechanism is configured to deliver flow rate (Ql) and flow rate (Q2) during an inhalation event, wherein (Ql) and (Q2) are different.

20. The electrohydrodynamic aerosol delivery device according to claim 19, wherein flow rate (Ql) is smaller than flow rate (Q2).

21. The electrohydrodynamic aerosol delivery device according to claim 19 or claim 20, wherein flow rate (Ql) precedes flow rate (Q2).

22. The electrohydrodynamic aerosol delivery device according to claim 19 or claim 20, wherein flow rate (Q2) precedes flow rate (Ql).

23. The electrohydrodynamic aerosol delivery device according to any one of claims 20 to 22, wherein flow rate (Ql) is in the range of 0.01 to 1 ml/h, preferably 0.01 to 0.1 ml/h.

24. The electrohydrodynamic aerosol delivery device according to any one of claims 20 to 23, wherein flow rate (Q2) is in the range of 0.5 to 10 ml/h, preferably 1.0 to 1.2 ml/h.

25. The electrohydrodynamic aerosol delivery device according to any one of claims 13 to 24, wherein the control unit is configured to increase or decrease the flow of liquid to the nozzle during an inhalation event.

26. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 25, wherein the potential difference applied between the orifice and the ground electrode is substantially constant for the inhalation event.

27. The electrohydrodynamic aerosol delivery device according to any one of claims 13 to 16, wherein the one or more parameters which are varied during the inhalation event is the potential difference applied between the orifice and the ground electrode.

28. The electrohydrodynamic aerosol delivery device according to claim 27, wherein the control unit is configured to control the power source to vary the potential difference applied between the orifice and the ground electrode during an inhalation event.

29. The electrohydrodynamic aerosol delivery device according to claim 28, wherein the variation of the potential difference applied between the orifice and the ground electrode may be an increase, decrease or pulsing of potential.

30. The electrohydrodynamic aerosol delivery device according to claim 30, wherein the potential difference applied between the orifice and the ground electrode is pulsed.

31. The electrohydrodynamic aerosol delivery device according to claim 30, wherein the pulsed potential is delivered at a frequency linked to one or more of:

one or more airflow characteristics through the device as a result of user inhalation; and the flow rate of liquid to the nozzle.

32. The electrohydrodynamic aerosol delivery device according to any one of claims 13 to 31, wherein the potential difference applied between the orifice and the ground electrode is in the range of from ±lkV to +10kV.

33. The electrohydrodynamic aerosol delivery device according to any one of claims 27 to 32, wherein the potential difference applied between the orifice and the ground electrode is varied during an inhalation such that a potential (vl) and a potential (V2) is applied during an inhalation event.

34. The electrohydrodynamic aerosol delivery device according to claim 33, wherein potential (VI) is in the range of from +lkV to ±5kV and potential (V2) is in the range from above ±5kV to lOkV.

35. The electrohydrodynamic aerosol delivery device according to any one of claims 13 to 34, wherein the parameters which are varied during the inhalation event are potential difference applied between the orifice and the ground electrode and flow of liquid to the nozzle.

36. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 35, wherein the control unit measures one or more airflow characteristics through the device as a result of user inhalation and in response thereto modifies one or more of:

potential difference applied between the orifice and the ground electrode; and

flow of liquid to the nozzle.

37. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 36, wherein variation of the one or more of the parameters which are to be varied leads to an aerosol having a particle size distribution with a maxima at less than 5 microns and a maxima at greater than 5 microns.

38. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 37, wherein variation of the one or more of the parameters which are to be varied leads to an aerosol having a particle size distribution with a maxima at less than 3 microns and a maxima at greater than 8 microns.

39. The electrohydrodynamic aerosol delivery device according to any one of claims 1 to 38, further comprising a liquid store in fluid communication with the liquid delivery mechanism.

40. The electrohydrodynamic aerosol delivery device according claim 39, wherein the liquid store is replaceable or re-fillable.

41. The electrohydrodynamic aerosol delivery device according to any one of claims 2 to 40, further comprising a mouthpiece arranged over the nozzle.

42. The electrohydrodynamic aerosol delivery device defined in accordance with the present description.