Technical Field

[0001 ] The present invention relates to methods, devices and systems for monitoring adherence to medication regimes for inhalers.

Background of the Invention

[0002] The invention is concerned with adherence monitors for dry powder inhalers in which the medicament is contained in a capsule which is perforated by the users (e.g. by a use of a piercing button on the inhaler) prior to the inhalation during which the medicament is delivered). These are often used in the treatment of respiratory diseases such as asthma, COPD, cystic fibrosis, and bronchiectasis. However, such devices may also be used to deliver other medications, for example for the treatment of pain, heart conditions, erectile dysfunction, diabetes, and other indications. The general term cap or cover will be used interchangeably to refer to all such covers and caps, however constructed, which serve to close or protect the mouthpiece when it is not is use, and are opened or removed when the inhaler is to be used.

[0003] One example of a dry powder inhaler dispensing medicament form a capsule is a Breezhaler™ (manufactured and marketed by Novartis AG), described in the U.S. Patent No. 8,479,730. Another example is the HandiHaler® manufactured and marketed by Boehringer Ingelheim Pharma GmbH & Co. KG). Other types of DPI are also known (e.g. Genuair® by Almirall).

[0004] A problem associated with the use of all medicament inhalers is poor adherence. Many studies have shown that users frequently do not take their medicament at the predetermined or prescribed times and/or in the required amounts. The consequences of this non-adherence can include reduced disease control, lower quality of life, lost productivity, hospitalisation and avoidable deaths. This represents a considerable cost to the users, as well as to the health system.

[0005] To address this problem, there are now available a number of adherence monitoring devices for use with medicament inhalers. The adherence monitors include dose detection means and means for transmitting the adherence data gathered, either wirelessly or otherwise, to a device such as, for example, a docking station, website, cloud computing network or a smartphone, tablet or personal computer (belonging to the user or a health professional). This adherence data may be transmitted in real time or at predetermined set times. Examples of patents which describe such technology are US Patent No. 6,958,691 (Anderson et al.), US Patent No. 8,424,517 (Sutherland et al.) and US Patent No. 8,342,172 (Levy et al.), US Patent No. 5,363,842 (Mishelevich et al.), US Patent No. 8,464,707 (Jongejan et al.), WO 95/07723 (Wolf et al.), US Patent Application No. 2014/0000598 (Sutherland), WO 2013/043063 (Sutherland) and WO 2015/030610 (Sutherland).

[0006] Numerous adherence monitoring devices on the market have been developed for pressurised metered dose inhalers (pMDI) (e.g., U.S. Patent Application No. 2014-0182584 by the present assignee; WO2014/004437 by Gecko Health Innovations) and various types of dry powder inhalers, such as Turbuhaler™ (e.g., U.S. Patent Application No. 20140182584 by the aplicant) or Diskus™ inhalers (applicant's SmartDisk™

[0007] To date however, there are few adherence monitors available that are suitable for use with a capsule inhalers. In particular, the applicant is not aware of any adherence monitors for the Breezhaler-type inhaler. The likely reason for the gap in the market is that the design and function of the Breezhaler-type inhaler poses several design challenges, especially in relation to: a) Secure yet releasable attachment of an adherence monitor to the inhaler.

When the cap is on the inhaler the outer surface of the inhaler has a relatively smooth curved surface with no or limited exposed ledges or ridges to easily fit clips; b) Ease of attachment of an adherence monitor to the inhaler, particularly for elderly, frail or weak users; c) Non-obstruction of the features required for user information (such as medication name and logo); d) Non-obstruction of functional features of the inhaler including:

(i) the movement of the capsule perforation element must be unimpeded;

(ii) the air inlets on the body of the inhaler must not be blocked or obstructed in any way; (iii) the pivoting mouthpiece must be unimpeded to allow insertion of a capsule containing a powdered medicament; and

(iv) the removal and replacement of the cap must be unimpeded; e) The inhaler has a flat base design to allow the inhaler to stand or rest in an upright position on a surface and it would be preferable that when the adherence monitor is attached to the inhaler they are still able to stand or rest in an upright position on a surface; and f) The inhaler includes a cap and it would be preferable if the presence, absence or both presence and absence of the cap on the mouthpiece could be detected. Such cap detection may assist in determination of usage errors such as medication waste.

[0008] The present invention resolves one or more of the above issues. It is an object of the present invention to address the absence of adherence monitors for Breezhaler-type inhalers on the market and give the patients and healthcare professionals the ability to track medication adherence in users of Breezhaler-type inhalers or at least provide a useful choice.

Summary of the Invention

[0009] In a first broad form the present invention provides an adherence monitor for a capsule inhaler.

[0010] According to one aspect, the present invention provides an adherence monitor for a medicament inhaler, the inhaler including

a body comprising

a recess for holding a capsule containing a powdered medicament; at least one button coupled to at least one perforation element for piercing the capsule loaded in the recess; a mouthpiece for operatively inhaling the medicament; and a cap configured to cover the mouthpiece, the adherence monitor including a housing configured to attach to the inhaler; and at least one sensor(s) configured to detect one or more of the following: attachment to the inhaler; compression or release of the at least one button; and a signal indicative of an inhalation.

[001 1 ] According to another aspect, the present invention provides an adherence monitor according for a medicament inhaler, wherein the at least one sensor(s) includes one or more of a pressure sensor, a pressure switch, a micro switch, a force sensor resistor, an acoustic sensor, an audible sensor, a motion sensor, a vibrational sensor, an optical sensor or a proximity sensor.

[0012] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is configured to detect the attachment of the housing to the inhaler.

[0013] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is an optical sensor including at least one infra-red emitter and at least one infra-red receiver configured to detect the attachment of the housing to the inhaler.

[0014] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is configured to detect compression or release of the at least one button.

[0015] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor includes at least one switch configured to detect compression or release of the at least one button.

[0016] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is configured to detect a signal indicative of an inhalation.

[0017] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler wherein the at least one sensor is configured to detect a signal consistent with the capsule being loaded into the recess, pierced or removed from the recess. [0018] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the housing is configured to releasably attach to the medicament inhaler in use.

[0019] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, further including a cap detection system configured to detect a position of the cap.

[0020] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the cap detection system is configured to detect an on and/or off position of the cap.

[0021 ] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the cap detection system includes one of the at least one sensors configured to detect a status of the cap of the inhaler.

[0022] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the cap detection system is configured to detect a cap on status, the cap on status being when the cap of the inhaler is positioned on or over the mouthpiece of the inhaler.

[0023] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the cap detection system is configured to detect a cap off status, the cap off status being when the cap of the inhaler is removed from the mouthpiece of the inhaler.

[0024] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is configured to detect the opening or closing of the mouthpiece, the opening of the mouthpiece configured to allow access to the recess in the body of the inhaler.

[0025] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the at least one sensor is configured to detect the presence or absence of the capsule within the recess.

[0026] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler, wherein the sensor for the detection of the presence or absence of the capsule within the recess includes at least one infrared emitter and at least one infra-red receiver. [0027] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler further including a processor wherein the processor operatively receives sensor data from the at least one sensor.

[0028] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler further including a communication means configured to send the sensor data to a secondary device, the secondary device including one or more of a smartphone, a tablet, a computing device, a server or a communication hub.

[0029] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler further including a user interface in a form of audio or visual reminders.

[0030] According to another aspect, the present invention provides an adherence monitor for a medicament inhaler further including an alert system, the alert system configured to send a signal to the user following detection of a predetermined event.

Brief Description of the Drawings

[0031 ] An illustrative embodiment of the present invention will be described with reference to the accompanying figures, in which:

[0032] Figure 1 is a perspective view of a prior art inhaler with the mouthpiece covered by the cap;

[0033] Figure 2 is a perspective view of a prior art inhaler showing the mouthpiece;

[0034] Figure 3 is a perspective view of a prior art inhaler showing the open mouthpiece of the inhaler and a recess for holding a medicament capsule;

[0035] Figure 4 is a perspective view of an embodiment of the present invention and of a prior art inhaler as shown in Figure 1 ;

[0036] Figure 5 is a front perspective view of the embodiment illustrated in Figure 4, with the adherence monitor attached to an inhaler and with the mouthpiece covered by the cap; [0037] Figure 6 is a rear perspective view of the embodiment illustrated in Figure 4, with the adherence monitor attached to the inhaler and the mouthpiece covered by the cap;

[0038] Figure 7 shows a top view of another embodiment of an adherence monitor according to the present invention;

[0039] Figure 8 shows another embodiment of an adherence monitor attached to an inhaler according to the present invention from which the cap has been removed;

[0040] Figure 9 shows the adherence monitor with inhaler attached illustrated in Figure 8, showing the cap removed and the mouthpiece fully opened to give access to the recess for holding the medicament capsule;

[0041 ] Figure 10 is a front perspective view of the adherence monitor with inhaler illustrated in Figure 9;

[0042] Figure 1 1 A shows a bottom view of the inhaler before the piercing of the medicament capsule; and

[0043] Figure 1 1 B shows a bottom view of the inhaler with the push buttons compressed to pierce the medicament capsule.

Detailed Description of the Invention

[0044] Throughout this specification, the terms "patient" or "user" or "person" or "patient usage", when used in relation to the use of a medicament delivery device, are to be understood to refer to any person that uses a medicament delivery device.

[0045] The present invention will be described in relation to various specific implementations, which it will be understood are intended to be illustrative and not limitative of the scope of the present invention. It will be appreciated, in particular, that various additional features and functions, indicators and the like may be included in monitors which implement the present invention. These may be selected for specific application at the option of the product designer. [0046] The present invention describes an adherence monitor for a capsule inhaler. Capsule inhalers dispense medication contained in a capsule for inhalation. A capsule for inhalation consists of an outer casing and the medication enclosed in the casing. The capsule may be a hard-shelled capsule, for example, a two-piece gel capsule. The capsule casing may be made using aqueous solutions of gelling agents, such as animal protein or plant polysaccharides or their derivatives, e.g. carrageenans, modified forms of starch and cellulose. Other ingredients may be added to the gelling agent solution, such as plasticizers, glycerine, colouring agents, preservatives, etc. Examples of the encased medication include ultra-long-acting beta-adrenoceptor agonists (e.g., indacaterol), long-acting muscarinic receptor antagonists (e.g., glycopyrrolate), either alone or in combination, or any other medication suitable for inhalation. Capsule inhalers dispense medication generally without use of a propellent, with each medication dose loaded before use. To release medication for delivery, the capsule is loaded into the inhaler, its casing is broken to expose the medication and the patient inhales the medication released from the capsule using deep inhalation to receive a full dose.

[0047] The following implementations will be described with reference primarily to Breezhaler™ capsule inhalers, as these are in widespread commercial use. However, the present invention may, with suitable modifications as will be apparent to those skilled in the art, be applied to other designs of inhalers presently known or yet to be developed. In particular, the present invention may be applied to other designs of capsule inhalers presently known or yet to be developed.

[0048] Similarly, whilst the discussion below is principally in relation to respiratory related medicaments, it is applicable to any use of inhaler devices, including by way of example only pain medication, diabetes, erectile dysfunction, or other conditions. The present invention is concerned with the monitoring of how the medication is used and dispensed, and should in no way be considered as limited to any particular medicament or condition.

[0049] As a general explanation, the implementations of an adherence monitor described are intended to be used with a medicament dispensing inhaler with a capsule chamber and/or recess, accessible through movement of a mouthpiece attached to the inhaler body by any form of a pivot point and a separate cap or cover. The devices include systems to detect that a dose has been dispensed, and to retain or communicate a record of this to a remote system, for example via Bluetooth® to a smartphone, tablet or other device. The intention is to automatically create a record of usage, to assist in clinical management. The devices may also provide reminders to the user, detect whether or not a dispensing device is attached, provide error indications, or provide other functions. [0050] The present invention is concerned with mechanical features and the location of switches in an adherence monitor. The electronics, communications, control software and the like may be in any suitable form, for example as is widely practiced and known in the art from the products available commercially from the applicant and related companies. The present invention does not impose any specific requirements in this regard. Reference should be had to, for example, the various references cited herein and incorporated by reference in order to provide further details of these aspects.

[0051 ] Referring to Figures 1 to 3 there is shown an existing medicament inhaler (Breezhaler™ inhaler by Novartis) device described in the U.S. Patent No. 8,479,730, the contents of which is incorporated herein in its entirety. It is acknowledged that Figures 1 to 3 are reproduced from figures 5, 1 and 2 respectively of U.S. Patent No. 8,479,730.

[0052] The inhaler device 1 includes a body 5 and a cap 120. The cap 120 is removable, replaceable and adapted to close off the mouthpiece 30 when the inhaler 1 is not in use. The cap 120 is configured to move in a substantially vertical direction, as indicated by arrow 2 in Figure 2, for removal and

replacement. The cap 120 ensures that the mouthpiece 30 remains clean, and free from dust and grime, and also ensures that no foreign objects can enter the mouthpiece 30, which may otherwise present a choking hazard.

[0053] The body 5 of the inhaler device 1 includes a recess 50 for holding a capsule containing a powdered medicament to be inhaled, a mouthpiece 30 that includes a coaxially disposed inhalation passage 70 that communicates with the recess 50 of the body 5. The body 5 has a pair of opposed spring biased pushbuttons 35 and 40 that each include at least one perforation means, perforation element or piercing element (not shown) for perforating or piercing the capsule when loaded in the recess 50. The medicament is released from the pierced capsule when air is drawn through the air passage(s) (not shown) into the recess 50 and swirled about therein. The mouthpiece 30 is pivotally attached to the edge of the body 5 so that it is pivotable between an open loading position and a closed dispensing position. In this example, in the closed dispensing position the mouthpiece 30 is in an upright or substantially vertical position. In the open loading position the mouthpiece is in a substantially horizontal position, as seen in Fig. 3. However, it is noted that in other forms the mouthpiece 30 of the inhaler 1 may be configured to move in other directions or ways such as slide or swivel in a sideways direction (not shown). [0054] To dispense the medicament from the inhaler device 1 , the user takes off the cap 120 from the mouthpiece 30, moves or pivots the mouthpiece 30 into it open position as shown in Figure 3 and places a capsule (not shown) containing a powdered medicament to be administered into the capsule chamber 45 of the recess 50. The user then moves or pivots the mouthpiece 30 back to its closed position ready for dispensing the medicament. The user pushes both push buttons 35 and 40 to activate a capsule perforation mechanism (not shown). The mechanism comprises a pair of needles that project inwardly from the push buttons 35 and 40. After the push buttons have been compressed and the capsule pierced, the user releases the pressure on them and the buttons are urged outward by a spring (not shown). Users administer the medicament by breathing out fully, inserting the mouthpiece 30 into the mouth, placing their lips and teeth around the mouthpiece and inhaling quickly and deeply. This action draws surrounding air into the inhaler device 1 through the air inlets 32 along the air passages (not shown), and into the recess 50.

[0055] The air passages (not shown) are positioned substantially tangentially with respect to the recess 50 so this rush of air into the recess 50 forms a vortex in the recess 50. This vortex in the recess lifts the perforated capsule out from the capsule chamber 45 and causes the capsule to spin rapidly about the longitudinal axis of the inhaler. The recess 50 has a substantially circular cross-section to accommodate the spinning capsule. The length of the capsule is slightly less than the diameter of the recess 50 so there are repeated impacts between the ends of the capsule and the side wall of the recess 50, which causes the powdered medicament from within the capsule to be drawn out through the perforations in the ends of the capsule, this being assisted by the spinning motion of the capsule itself. The powdered medicament is entrained with the air passing through the perforated plate 65 and along the inhalation passage 70 of the mouthpiece 30. The walls that define these passages, recesses and tube are formed with smooth curves to minimise air resistance and thereby minimise the effort that is required of the user to inhale the medicament. The perforated plate or grid 65 prevents the capsule being inhaled up the tube 60.

[0056] This inhalation action may be repeated. When the capsule has been spent, which is more easily seen when the capsule casing is transparent, the user moves the mouthpiece from its closed (dispensing) position to its open (loading) position and discards the spent capsule. The device is then ready to be reloaded with a fresh capsule containing the desired medicament and reused.

[0057] Referring to Figure 4, there is shown the inhaler device 1 and an adherence monitor 402 according to an embodiment of the present invention. The adherence monitor 402 is housed within a second housing 403, which is configured to releasably attach to the inhaler device 1 . The second housing 403 is adapted to attach to or couple with the body 5 of the inhaler 1 , gripping the front 10 and the back 15 of the inhaler 1 , without interference with the operation of: the push buttons 35 and 40; the mouthpiece 30 (as shown in Figures 2 and 3); the air inlets 32; or the pivotal movement of the mouthpiece 30 to allow opening/closing and access to the recess 50 (as shown in Figures 2 and 3).

[0058] In some embodiments, the second housing 403 may attach to the inhaler 1 by friction, mechanical coupling, adhesive coupling or other resealable coupling methods. Ensuring that the second housing 403 retains inhaler 1 securely without additional tools, adhesives or tape was an obstacle.

[0059] In some forms and as seen in Figure 4, the second housing 403 may include a bottom base 41 1 with an upright front and back walls 412, 414 extending therefrom. The inhaler 1 is inserted between the front wall 412 and back wall 414 and rests upon the bottom base 41 1 (see Figures 5 and 6). The front and back walls 412, 414 are preferably configured such that they will not impeded the movement of the mouthpiece 30 of the inhaler 1 in use. For example, the maximum height of the back wall 414 may be shaped to still allow the opening of the mouthpiece 30 for insertion of a capsule of medication (see Figures 8 and 9). The heights of the front wall 412 and the back wall 414 may be different as shown. Alternatively, the front and back walls may have similar heights (not shown). The front wall 412 and back wall 414 are configured to provide sufficient surface area in contact with the outer surface of the inhaler body 5 to retain the adherence monitor 402 on the inhaler 1 .

[0060] In some embodiments one or more retainers 404 may be provided on the inner surface of the adherence monitor 402. In the embodiment illustrated in Figure 7 there are four retainers 404, two provided on the front wall 412 and two on the back wall 414. To ensure secure yet releasable attachment seal elements (such as toroidal seal) may be bonded onto the front and back walls 412 and 414 respectively.

[0061 ] In other embodiments, the adherence monitor 402 may consist of two portions, such as front and back portions or two side portions, connected by a hinge and attachable to the inhaler device 1 by clamping them onto the body 5 (not shown).

[0062] In other embodiments, the adherence monitor 402 may consist of at least two portions, such as front and back portions, which can be connected via an internal spring-loaded releasable catching latch and thus fitted around the body 5 of the inhaler device 1 (not shown).

[0063] In other embodiments, the adherence monitor 402 may attached to the body of the inhaler 5 using flexible, elastic material (not shown).

[0064] When fitted onto the inhaler 1 , the adherence monitor 402 permits the user to dispense the medicament as described above, without functionally interfering with the cap 120, mouthpiece 30, air inlets 32, capsule recess 50, or push buttons 35 and 40.

[0065] The adherence monitor 402 may include an inhaler sensor 405 for detecting that the adherence monitor 402 is attached to the inhaler 1 .

[0066] The inhaler sensor 405 may be a mechanical, electromechanical or electronic sensor. The inhaler sensor 405 may be an optical infrared (IR) sensor that detects the presence or absence of the base or wall of the inhaler 1 within a certain distance by generating data output based on an optical signal received. The location of the inhaler sensor 405 as shown in Figure 4 is indicative only and the inhaler sensor 405 may be in or on any other location of the adherence monitor 402 provided that the inhaler sensor 405 can detect when the inhaler 1 is inserted into the adherence monitor 402. Preferably the inhaler sensor 405 is provided within or on the base 41 1 , front wall 412 or back wall 414.

[0067] The inhaler sensor 405 may include an infra-red light emitter and infra-red light receiver positioned in such way that the optical signal emitted from the emitter is reflected off the base or the wall of the medicament inhaler and received by the receiver. The inhaler sensor 405 may be located in any position on or within the base 41 1 , front walls 412 or back wall 414 provided that the optical signal emitted by the IR sensor is blocked or altered by the body of the inhaler 1 once it has been inserted into the adherence monitor 402. The data output of the receiver is processed by the processor to determine if the output is consistent with 'inhaler in' or inhaler out' parameters recorded in a memory database.

[0068] The adherence monitor 402 may include at least one dose preparation sensor 407 for detecting compression or release of the push buttons 35, 40. In some forms the at least one dose preparation sensor 407 is a micro-switch and the adherence monitor 402 includes at least one micro-switch 407 to detect the compression or release of at least one of the push buttons 35, 40. In Figure 4 the adherence monitor 4 is shown having two micro-switches 407, one to detect compression or release of each of the buttons 35, 40.

[0069] Figures 1 1 A and 1 1 B show views of the base of the inhaler which illustrate the position of the push buttons 35 and 40 prior to the compression by the user (Figure 1 1 A) and at the point when the user pierces the capsule (Figure 1 1 B). When the user pushes the push buttons inwardly towards the recess 50 (shown in Figure 3), the base 435 of the push buttons 35 and the base 440 of the push button 40 engage with one of the micro-switches 407, causing the micro-switch to open or close. The opening or closing of the pair of the micro-switches 407 is logged as a compression of the push buttons 35 and 40.

[0070] Conversely, when the push buttons 35 and 40 are released they have the opposite effect on the micro-switches 407, i.e. they close an open switch or open a closed switch. The change in signal from the pair of the micro-switches 407 is logged as release of the push buttons 35 and 40.

[0071 ] In some embodiments of the present invention, the dose preparation sensor for detecting the compression or release of the push buttons may be a force resistor sensor, an optical sensor (e.g., a IR sensor, a proximity sensor, a colour sensor), or any other type of sensor or a combination of different types of sensors, each adapted to detect a change in the position of at least one of the push buttons 35 or 40, characteristic of the compression or release of the button. In some forms, the dose preparation sensor and the inhaler sensor may use the same sensor configured to detect both the presence of the inhaler 1 inserted into the adherence monitor 402 and the compression or release of at least one button 35, 40 of the inhaler 1 .

[0072] In some forms the dose preparation sensor may include a vibrational, audio or pressure sensor. Such sensors are configured to determine the differences between the presence or absence of a dose of medicament being in the recess 50. The sensor may determine the presence or absence of a capsule of medicament in the recess 50 when particular actions occur, including (a) the buttons 35, 40 are compressed or pushed; (b) a capsule is pierced; (c) the user inhales on the mouthpiece 30; or (d) any combinations of (a) to (c). Such characterisation may enable determination of the medication preparation status for delivery of dose of medicament to facilitate improved compliance monitoring by the adherence monitor 402.

[0073] Further, the adherence monitor 402 includes an acoustic sensor (not shown), that may be positioned on a printed circuit board (not shown) integrated into the second housing 403. The acoustic detection of actuation and/or inhalation is used in addition to the mechanical switch triggers to determine medication delivery events (both medication dispensing and inhalation). Preferably the acoustic sensor is placed in or near the base of the second housing 403 or in proximity of air inlets 32, but this location is intended as an example only and is not intended to be limiting. The acoustic sensor may be located in any suitable position within the second housing 403. The acoustic sensor is not in direct contact with the inhalation pathway or medication flow, but held within the second housing 403 to ensure that there is no interference with the flow of the medication into the patient's airways.

[0074] In some examples of the invention, a microphone portion of the acoustic sensor may be provided within the front wall 412 or back wall 414 or the base 41 1 of the adherence monitor 402. For example, referring to Figure 4, arrow 416 indicates one possible location of a microphone which may form a part of an acoustic sensor.

[0075] Preferably, the acoustic sensor consists of a circuit that includes one or more microphones, an amplifier and a filter. In one example of the invention, the microphone may be an acoustic microphone, characterised by a small form, surface mount fit and low power consumption and analog output (Knowles Acoustics SPU0410HR5H-PB micro-electro-mechanical system (MEMS)). Alternatively, and/or additionally, the microphone may have an analog output or digital output. In other embodiments, the acoustic sensor may use multiple sensors. Analog filtering and a low power dual operational amplifier may be used to amplify the signal. A two stage gain control may be configured to control gain for the amplifier. The output of the microphone is coupled into the Electronics control module (ECM or processor) (described in more detail below) via an ADC input. The microphone and amplifier may be powered via a ECM GPIO pin, allowing it to be powered up, preferably for a short period of time, when medication loading / actuation is detected. Preferably, the microphone and amplifier are in a default powered down state at all or most other times to maintain battery life. However, in some aspects the microphone and amplifier may be provided a continuous or periodic supply of power.

[0076] The acoustic sensors may be configured to generate output signals at prescribed times. This may include generating signals intermittently, periodically (e.g. at a sampling rate), continuously, continually, at varying intervals, or otherwise. The sampling rate may be at, for example, 2-10 milliseconds (ms), such as 5 ms or any suitable smaller or greater sampling rate. [0077] Depending on the design of the inhaler, a frequency peak characteristic of inhalation may be approximately 1 -25 kiloHertz (kHz), preferably 10-13 kHz. Inhalation through Breezhaler inhaler (with loaded capsule) generates a flat frequency profile in the range of approximately 8-12 kHz, such as approximately 10 kHz. Preferably the signal is processed using the signal power envelope rather than the frequency signal directly. For that purpose, the signal is rectified to remove the DC offset and smoothed. In one preferred simple implementation, a high pass filter or similar arrangement allows for the power levels at the targeted frequencies to be measured. This allows for an inhalation event to be identified as an increase in signal relative to the background level. More complicated implication methods require a detailed frequency spectrum or analysis to be performed and would require increased processor power and memory.

[0078] The processor is programmed to sample the ADC output (bits) at a chosen sampling rate and to measure the signal energy. Positive actuation and positive inhalation results are triggered by the algorithm when the signal exceeds a predetermined threshold for a predetermined period of time threshold. This ensures that the positive results cannot be triggered by an intense burst of signal for a short time period that is too short to be a valid actuation or inhalation.

[0079] The acoustic sensor may also be adapted to detect other acoustic signals which are characteristic of, for example, removal of the cap 120, opening of the mouthpiece 30, insertion of a capsule, piercing of the capsule, removal of the used capsule and closing of the mouthpiece or cap. Each of these usage events generates a characteristic acoustic signature, which can be detected by the acoustic sensor, converted into a digital signal as described above and logged by the ECM. These characteristic acoustic signatures may also include specific frequency peaks.

[0080] While the primary component of the sound generated by turbulent airflow is in the 1 -25kHZ range, in the case of capsule inhalers a lower frequency component is detected, for example at 1 -100 Hz level. Such lower frequency may be used to detect the capsule movement within the capsule recess or capsule holder. Thus, the acoustic sensor may be further adapted to detect signal characteristic of movement of the capsule within the capsule recess 50 and to detect presence or absence of capsule during the inhalation, or proper or failed perforation of the capsule.

[0081 ] It will be appreciated that any suitable acoustic sensor adapted to adequately detect the required frequency range and provide a corresponding output may be used. For example, suitable piezoelectric devices or other forms of acoustic sensors.

[0082] In other forms the adherence monitor 402 is adapted to detect inhalation through detection of motion of the inhaler 1 or vibrations generated by the spin of the medicament capsule in the capsule recess 50. The adherence monitor 402 may include various vibration or motion sensors known in the art, e.g., an accelerometer, a gyroscope, a magnetometer, an acceleration switch, an altimeter, a tilt switch, or any other motion and orientation sensing sensor that is known in the art or hereinafter developed. The inclusion of vibration or motion sensors allows detection of movements or orientations of the inhaler 1 that are characteristic of various steps of inhaler usage. The signals from the sensor are processed by the ECM using analytical algorithms and reference tables. The results of the analysis are logged by an ECM and can be transmitted to remote computing devices, as described below.

[0083] The adherence monitor 402 may further comprise a cap detect sensor. The cap detect sensor may be in the form of a cap detect switch 406 as shown in Figure 4. The switch is located on the inner wall of the second housing 403 which abuts to the cap 120 when it is placed on the mouthpiece 30. The switch 406 is positioned so that when the cap 120 is placed on the mouthpiece 30, the cap 120 actuates the switch 406. The switch 406 is configured to be opened or closed by the action of cap removal, and, when the cap 120 is replaced, the switch 406 is configured to close or open (opposite to the response to cap removal). Following each change of switch status, an appropriate signal is sent to an ECM. The switch 406 is preferably an electronic or electromechanical switch, although any type of switch is within the scope of this invention.

[0084] In other embodiments, the cap detect sensor is a surface mount detector switch combined with a mechanical lever. The arrangement and construction may be such that the cap 120 actuates the switch when the cap is on the mouthpiece 30, and deactivates the switch when the cap 120 is off (or removed from) the mouthpiece 30, or vice versa.

[0085] In another embodiment, the cap detect sensor may be optical, whereby a beam of light (e.g., IR light) may detect the presence of the cap 120 when it is on the mouthpiece 30 and the absence of the cap 120 when the cap 120 is removed from the mouthpiece 30. It will be understood that the open / closed states indicated may be reversed. [0086] In some forms the adherence monitor 402 may directly monitor: (a) when a cap 120 is in the Off status; (b) when the cap 120 is in the On' status; or (c) both the Off and On' status of the cap 120. If (a) or (b) are directly monitored, then the opposing status may be determined as occurring when the monitored status is not detected. In some forms the adherence monitor 402 may detect whether the cap 120 is On' or 'off using a sensor positioned on the adherence monitor 402.

[0087] The cap detect sensor may include a plurality of sensors configured to detect a range of parameters related to the removal and replacement of the cap 120. The plurality of sensors may include different types of sensors including one or more of the sensors referred to herein, e.g. acoustic, pressure, vibrational, optical and force pressure sensors. The ECM may collate the information received from the plurality of sensors to improve accuracy of the cap detection system.

[0088] In some forms the adherence monitor 402 may monitor or detect whether the cap 120 is On' or 'off the mouthpiece 30 at the time of delivery of the dose of medicament. Alternatively, the adherence monitor 402 may continuously monitor or monitor on a regular basis the status of the cap 120.

[0089] In some forms the adherence monitor 402 may monitor or detect whether the cap 120 is "off" by detecting movement, pivoting or opening of the

mouthpiece 30 instead of or in addition to the removal of the cap 120, as the mouthpiece 30 may only be opened after removal of the cap 120.

[0090] The adherence monitor 402 may be configured to distinguish when a dose of medicament is delivered and the cap 120 is 'on' from when a dose of medicament is delivered and the cap 120 is 'off. Thus, the adherence monitor 402 may monitor or detect and record when correct delivery of a dose of medicament has been delivered.

[0091 ] In yet further embodiments, the cap detect sensor may be an infrared (IR) optical sensor or a proximity sensor or any other suitable sensor. For example, the sensor may include a sensor as described for use in the compliance monitor described in International Application number PCT/NZ2015/000037 published as WO 2015/1 74856 on 19 November 2015, the contents of which is incorporated herein in its entirety.

[0092] The cap detect sensor may include an optical sensor including: a) at least one light transmitter able to transmit an optical signal, b) at least one light receiver able to receive an optical signal, c) the arrangement and construction being such that movement of the

cap120 alters the optical signal(s) whereby the optical sensor is able to determine the position of the cap 120.

[0093] For most medicament inhalers with a cap, the attachment of the cap on to the mouthpiece results in an audible sound, such as a click, as a cap retaining feature engages with a complimentary retaining feature provided on the

medicament inhaler. The disengagement of these retaining features may also provide a distinctive audible sound or vibration.

[0094] In some forms, the adherence monitor 402 may include at least one mouthpiece sensor adapted to detect and log the open or closed state of the mouthpiece 30. For example, as shown in Figure 6, the back wall 414 of the adherence monitor 402 may include a mouthpiece sensor located in position 418 which is adapted to detect when the mouthpiece 30 is fully open. The sensor may be any form of a switch actuatable by the contact between the hinge 75 or adjacent region (shown in Figure 3), connecting the body 5 of the inhaler 1 and the movable mouthpiece 30, with the protrusion 420. Alternatively, the mouthpiece sensor may be a contactless sensor such as an optical sensor (not shown). As mentioned above, detecting the opening of the mouthpiece 30 may also indicate that the cap 120 has been removed.

[0095] As mentioned above, the adherence monitor 402 includes an ECM (not shown) which is included within the second housing 403. The ECM is configured to process and/or cause storage and/or transmission of adherence data relating to patient usage of the inhaler 1 . The ECM is also configured to process data relating to one or more of the following: inhaler in/out status, compression or release of the push buttons 35 and 40, inhalation detection, cap 120 removal/replacement from/onto the mouthpiece 30, movement/pivoting/opening of the mouthpiece 30, inhalation or capsule status or any other usage event described herein. The ECM may include or be coupled with a communication means (not shown) within or on the second housing 403. The ECM may also include a memory described in more detail below.

[0096] The ECM may be configured to cause the information relating to the usage events to be recorded in the memory. The information may include inhaler-in log, type of inhaler, time stamp for the cap on/cap-off event, time stamp for mouthpiece open /closed event, time stamp for inhalation event, etc. Preferably, the ECM may be configured to analyse usage events to determine that a valid medicament dose delivery event has or has not occurred. Preferably, the ECM may be configured to detect when a usage error has occurred.

[0097] In some forms, the ECM may be configured to determine the likelihood of a medicament dose delivery event occurring based on the amount of time that the cap is removed from the mouthpiece (or is in the Off state), before being replaced onto the mouthpiece (changed to the On' state).

[0098] In other forms, the ECM may be configured to, based on combinations of sensor data received by the ECM, determine if the inhalation occurred with or without the medicament capsule being inserted or with or without the capsule being pierced by the user prior to inhalation.

[0099] Testing by the applicants has shown that it is unlikely that a person could remove the cap from the mouthpiece, insert a medicament capsule, pierce the capsule and deliver a dose of medicament, and subsequently replace the cap, in less than three seconds. Accordingly, in some forms the ECM may determine that a dose of medicament may have been dispensed if the cap is removed from the mouthpiece for longer than a predetermined period of time, such as two, three, four, five, or more seconds. Although, other sensor signals processed by the ECM are likely to be required to confirm that a dose of medicament has been dispensed.

[00100] Hence, if a person inadvertently dislodges the cap from the mouthpiece, and immediately replaces the cap, in (for example) less than three seconds, then the ECM will in this implementation determine that a medicament dose delivery event has not occurred.

[00101 ] Preferably, the ECM may be configured to cause a medicament dose delivery event to be stored in the memory. The ECM may also be configured to receive and store in the memory outputs from any other sensors connected to the ECM.

[00102] As well as the ECM being capable of processing data relating to any usage event, the ECM may also be adapted to monitor and/or manipulate and/or store and/or transmit any type of sensor or adherence data relating to patient usage of the medicament inhaler via the communication means (not shown). Such ECM's will be familiar to those skilled in the art of adherence monitoring technology for medicament inhalers. The ECM may also determine and/or store other related data, for example time information, location, communications connection status, operation data relating to the monitor, and data as known in the art. The communication means allows communication of data detected or stored by the ECM to be transmitted or communicated to a secondary device such as smartphone, tablet, computing device, server, communication hub or other such devices.

[00103] In some forms the adherence monitor 402 may be configured to provide an alert or alarm system to identify when a usage error is identified, (e.g., capsule has not been inserted prior to inhalation, capsule has not been pierced prior to inhalation). The alert or alarm may act as a reminder to the user to place a capsule in the recess 50 or pierce the capsule and administer the medication again. The alert or alarm may be configured to provide a signal. The signal may be provided in one or more form such as an audible, visual or tactile form. For example, the signal may be a light, LED, audible signal, vibrational signal or the like. The signal may be provided directly on or by the adherence monitor 402 or may be sent to an electronically coupled device such as a mobile phone, other form of mobile computing device or computer.

[00104] In some forms the alert or alarm may be configured to activate following detection of one or more predetermined events. The predetermined events may include one or more of the detection of the cap 120 being removed (detected cap Off status); empty capsule within the recess 50; detection of administration of a dose of medicament (correctly or incorrectly); reminder to take next dose of medication; or other similar events. For example, the alert or alarm may be configured to activate following expiry of a predetermined periods of time after the predetermined event has occurred. The predetermined period of time may be between 1 second and 60 minutes, such as 5, 10, 20, 30, 40, 50, 60, 90, or 120 seconds; 1 , 2, 3, 4, 5, 10, 20 or 30 minutes or at any other similar time limit. The setting parameters for the alert or alarm may be configurable by the user. For example, the user may be able to select or set one or more of the predetermined periods of time; the types of predetermined events, the type of alert of alarm or to turn off the alert or alarm.

[00105] The ECM is adapted to perform one or more of monitor, manipulate, store or transmit adherence data relating to patient usage of the inhaler 1 . The electronic controls and sensors may be distributed throughout the device. The ECM may be in the form of a suitable microprocessor device. [00106] The second housing 403 is releasably attachable to the inhaler 1 , consequently the adherence monitor 402 may be portable and/or reusable across multiple inhalers of the same kind.

[00107] In some forms the adherence monitor 402 may include a dose detection means in a form of a switch or sensor located in or on the second housing 403 and configured to detect that the dose of the medicament is dispensed. The dose detection means may include one or more of an acoustic sensor, vibrational sensor, thermistor, pressure sensor, pressure switch, force sensor resistor, audible sensor, optical sensor or proximity sensor, mechanical switch. Depending on the type of switch or sensor selected, different signals may be used to detect a dose detection being dispensed: change in pressure, temperature, volume, visible or IR light intensity, etc.

[00108] When a dose of medicament is dispensed and the dose detection switch (not shown) is actuated, an appropriate signal is sent to the ECM, where the dispensing of the dose is recorded, and the date and time of the dispensing of the dose is also recorded. Such a dose detecting apparatus has been previously described in our patent application WO2013/043063, which is incorporated herein, in its entirety, by reference.

[00109] The use of ECM's, in conjunction with adherence monitors for medicament delivery devices, are well known, and it is not intended therefore to describe them in any significant detail herein. For example, these systems are in general terms in commercial use in products available from the present applicant and related companies, as well as disclosed in the applicant's prior patent filings, for example those incorporated by reference herein. An example of an adherence monitor, used in conjunction with an ECM and/or transmitter can be found in our US Patent No. 8424517 and our US Patent Publication No. 2014/0000598, the contents of which are incorporated herein in their entirety.

[001 10] The ECM is powered by a battery, and either a rechargeable or replaceable battery may be used. The ECM and/or the adherence monitor may alternatively be powered by any suitable alternative means, for example a kinetic charger, or by solar power, or inductive charging.

[001 1 1 ] The ECM stores and transmits the adherence data gathered, so that analysis can determine if the user has used the inhaler correctly and/or incorrectly. The inhaler use logs generated in the adherence monitor are uploaded into smartphone application, a PC or a central communication hub, and through those into a web based server. In some embodiments, the inhaler use logs may also be uploaded from the adherence monitor directly into a web based server.

[001 12] Adherence monitor 402 includes a memory, the memory being in communication with the ECM. In some embodiments, a volatile type computer memory, including for example RAM, DRAM, SRAM, may be used. In such instances, the adherence monitor may continually transmit information to the computing device external to the adherence monitor or medicament delivery device. In other embodiments non-volatile memory formats may be used, including for example ROM, EEPROM, flash memory, ferroelectric RAM (F-RAM), optical and magnetic computer memory storage devices, and others.

[001 13] The adherence monitor 402 may also include indication means, such as LED to indicate an event and/or to alert the user if the ECM determines that the user has used the inhaler correctly and/or incorrectly. The indication means may be utilised to alert the user if they have attempted to dispense a dose of medicament with the cap 120 still attached. Alternatively, the indication means may be used to alert the user if medication has not been dispensed within a certain timeframe, e.g. every 1 2h or 24h.

[001 14] The indication means may be in the form of one or more LEDs, or in the form of some other visual and/or audio and/or vibrational indicator. Adherence monitor 402 also includes a multi-function user button for monitoring and controlling several aspects of operation. For example, pushing the button once may result in a green light showing if the adherence monitor 402 is fitted to the inhaler 1 correctly, and in normal working order. Conversely, a red light may indicate a problem. Pushing the button twice may provide for another aspect of the adherence monitor to be checked or reported, and furthermore pushing and holding the button may result in yet another function or check being done.

[001 15] Referring to Figures 5 and 6 the adherence monitor 402 may include one or more of a battery status button 408, a reminder button 409 or a pairing button 410.

[001 16] The adherence monitor 402 may in some forms also include a user interface (not shown) enabling the user to access data recorded or received by the adherence monitor and also change the settings of the adherence monitor (for example, date/time, visual/audio alert settings). The user interface may also be used to access any data received (or transmitted) by the adherence monitor or to control the upload of the data from the adherence monitor to an external electronic device. The user interface may be located in the exterior surface of the second housing 403.

[001 17] The embodiments of the adherence monitor 402 and/or the ECM described herein may be able to monitor any type of non-dose counting information relating to the operation of the inhaler 1 , and/or patient usage of the inhaler 1 . For example, the ECM may include a real-time clock (or be in electronic communication with one) to enable the adherence monitor 402 to record a date and time for each dose of medicament dispensed. The ECM may be calibrated to compare the actual doses dispensed against the table of pre-set dosage times and, if the dose is not dispensed at the pre-set time, alert the user that a dose is due.

[001 18] Furthermore, and for example only, adherence monitor 402 and/or the ECM may also be able to monitor criteria such as geographical location, temperature, humidity, the orientation of the inhaler 1 , the condition of the medicament, the amount of medicament left, the condition of the battery or whether it is installed, the flow or pressure of the user's inhalation, an audio sensor for detecting inhalation or for determining if the main body portion has been rotated with respect to the base portion, and so on. To this effect, the ECM may include an audio or optical inhalation sensor, thermistor sensor or accelerometer, or be connected to a GPS (e.g. the adherence data from the smartphone paired with the adherence monitor 402 may be matched with the GPS data relating to the location of adherence events received by the smartphone).

[001 19] As mentioned above the adherence monitor 402 and/or ECM may also include a communication device for transmitting the adherence data. In one embodiment, this may be a USB port (not shown) located on the second housing 403 of the adherence monitor 402. Any other suitable wired connections or ports may be used.

[00120] Alternatively, and/or additionally, the adherence monitor 402 and/or ECM may be provided with a wireless transmitter and/or a wireless transceiver e.g. Bluetooth Low Energy module to be able to transmit and/or receive data respectively. Any other suitable wireless technology known in the art may be used, including for example Wi-Fi (IEEE 802.1 1 ), Bluetooth®, other radio frequencies, Infra-Red (IR), GSM, CDMA, GPRS, 3G, 4G, W-CDMA, EDGE or DCDMA200 or similar.

[00121 ] The data may be transmitted to a remote computer server or to an adjacent electronic device such as a smart phone or electronic tablet. The adherence monitor may be paired with a smartphone loaded with a software application which allows the smartphone to access, process, and/or present the data collected by the adherence monitor. The smartphone may be configured to transfer the data obtained from the adherence monitor to a web services platform. The data may be transmitted in real time, manually or at predetermined set times.

[00122] While the embodiments described above are currently preferred, it will be appreciated that a wide range of other variations might also be made within the general spirit and scope of the invention. The adherence monitor 402 has been described as including a number of different types of sensors to detect different aspects related to the inhaler 1 . For example, inhaler sensor, dose preparation sensor, cap detect sensor, mouthpiece sensor and other such sensors. The adherence monitor may include combinations of the different types of sensors described and should be understood not to be limited to having to include all the different types of sensors.

[00123] For example, other types of switches may be used to detect the absence or presence of a cap on the mouthpiece of the inhaler: e.g. any type of carbon pill, tack switch or detector switch may be used. Some examples of suitable switches include: http://wvtf.diaikey.co.nz/product-detail/eri/ESE-13V01 D/P13356SCT- ND/822292; http^/www.di ikey.co.nz/product-detail/en/ESE-16J001 /P14266SCT- D/2193025; or :/ M^

lZ59d iD 227^

[00124] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

[00125] All patent and other references noted in the specification, including websites, are hereby incorporated by reference in their entirety.