Smart Valve Holding Chamber

Abstract

To provide a medication delivery system with a holding chamber capable of delivering multiple doses of medication from a metered dose inhaler. [Solution] The holding chamber has an actuation detector, a flow detector, and / or a metered dose inhaler identifier operative to identify a metered dose inhaler coupled to the holding chamber, and a display. In another embodiment, a user interface for administering medication includes a medication administration device, a mask portion having a sealing portion with a contact sensor responsive to contact with a user, and an indicator in communication with the sensor to provide feedback. In another embodiment, a medication delivery system includes a housing defining a flow channel and a valve disposed within the flow channel, the valve movable between a first and a second configuration in response to flow, the valve being comprised of an electroactive polymer, the valve being reconfigured between a first and a second resistance state in response to an electrical stimulus.

Description

[Technical Field]

[0001] This application relates to devices and systems used in the field of pulmonary aerosol drug delivery in metered dose inhalers or metered dose inhalers (MDIs) and valved holding chambers (VHCs), and in particular to devices and systems that improve patient compliance with drug therapy and provide feedback to users, prescribers, or payers regarding proper inhalation technique and the completion of treatment or procedure.

[0002] REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 338,798, filed May 19, 2016, and U.S. Provisional Patent Application No. 62 / 366,327, filed July 25, 2016, which are incorporated by reference in their entireties. [Background technology]

[0003] VHC and MDI systems are typically used to treat conditions such as asthma, COPD, and cystic fibrosis. Patients being treated for such conditions may have poor adherence to medication or treatment regimens, practice improper device technique, and / or fail to receive feedback regarding dosage reliability. These types of problems can result in additional costs for the healthcare system and suboptimal patient outcomes. Summary of the Invention [Problem to be solved by the invention]

[0004] Medication compliance is often difficult to monitor, yet this information is extremely important to healthcare providers. Currently, there are no methods for actively monitoring patient use of VHCs, and despite the recent advent of smart inhalers, most MDIs are unable to independently monitor and communicate drug use. Therefore, there is a need for VHCs that can monitor drug use and provide feedback to users and healthcare providers. [Means for solving the problem]

[0005] Upon insertion of an MDI into the VHC, the system identifies the MDI inserted within the VHC. As the user takes a trial breath, the system monitors flow and provides the user with feedback regarding their technique, including whether they are breathing too fast or whether their breath-holding is adequate. During this trial phase, the system can inform the user of the most appropriate time in their breathing cycle to activate the MDI.

[0006] Once the MDI is activated, the system detects and records the activation and the duration between activation and the first inspiratory flow. This information is used to provide coordinated feedback following the current therapy or procedure and / or at the start of the next therapy or procedure. At the end of inspiration, a second timer can be started, which measures the user's breath-hold duration. This information can be used to provide further feedback before the next breath-hold or before the next therapy.

[0007] Following MDI actuation, the system can determine when the user has received their full dose of medication. This can be accomplished by measuring flow rate and integrating over the total volume delivered, or by other means. At the end of treatment, the user is notified, and the system, by default, waits for a second actuation of the MDI. If too much time passes without actuation, the system will turn off. Additionally, if the user removes the MDI, the program will exit in one embodiment.

[0008] Various methods can be used to relay information and provide feedback to the user. LEDs, LED boards, 7-segment displays, LCD and / or OLED screens can be used to provide visual feedback. Audio feedback can also be used, with the option to mute the sound at the user's discretion. Haptic feedback can also be used; for example, the VHC vibrates when excess flow is removed. For example, an application program or website can be used to display the information on the screen, or on a mobile device, remote computer, or other user interface.

[0009] Various systems and devices improve patient adherence, improve device technology, and provide dosage certainty. These aspects help reduce costs to healthcare systems and providers (payers) by ensuring proper adherence. In addition, healthcare providers (prescribers) armed with reliable information about adherence and usage can utilize patient-specific data to make informed decisions regarding treatment protocols and modifications. Patients receive maximum benefit from their treatment, further reducing out-of-pocket costs.

[0010] The foregoing paragraphs have been provided by way of general introduction and are not intended to limit the scope of the invention as set forth in the claims. The various preferred embodiments, together with other advantages, will be best understood by reference to the following detailed description, taken in conjunction with the accompanying drawings, in which:

[0011] The figures show various embodiments of the medication delivery system, block / flow diagrams and methods of use and assembly thereof. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a flow diagram illustrating a feedback loop for patient adherence, therapy or treatment protocol, and payer interaction. [Figure 2] 1 is a flow diagram illustrating the use and feedback loop for a smart VHC device. [Figure 3] FIG. 1 is a side view of one embodiment of a smart VHC. [Figure 4] FIG. 10 is a side view of another embodiment of a smart VHC. [Figure 5A] FIG. 1 shows an actual image of a medication container. [Figure 5B] FIG. 1 shows a grayscale image of a medication container. [Figure 6] FIG. 5B is a pictorial representation showing proper identification of the medication container shown in FIG. 5A. [Figure 7] 1A-1C are side views of various alternative embodiments of the smart VHC. [Figure 8] FIG. 10 is a graph showing photodetector output versus time for MDI operation. [Figure 9] FIG. 10 is a side view of another embodiment of a smart VHC. [Figure 10] FIG. 1 is a graph showing the relationship between power output and flow rate for various MDI configurations. [Figure 11] 1 is a schematic diagram of various inputs / outputs associated with the use of an MDI. [Figure 12] 1 is a flow diagram illustrating MDI usage and feedback loops. [Figure 13] FIG. 10 is a side view of another embodiment of a smart VHC. [Figure 14] FIG. 10 is an end view of another embodiment of a smart VHC. [Figure 15] FIG. 10 is a graph showing the correlation between valve opening and flow rate. [Figure 16] 1 is a diagram illustrating various controller inputs. [Figure 17] 1 is a flow diagram illustrating MDI usage and feedback loops. [Figure 18] FIG. 10 is a side view of another embodiment of a smart VHC. [Figure 19] FIG. 10 is a partial side view of another embodiment of a smart VHC. [Figure 20] FIG. 10 is a graph showing the relationship between pressure sensor output and time regarding MDI operation. [Figure 21] FIG. 1 is a graph showing pressure change versus time during MDI actuation and inspiration. [Figure 22] 1 is a diagram illustrating various controller inputs. [Figure 23] 1 is a flow diagram illustrating MDI usage and feedback loops. [Figure 24] FIG. 10 is a side view of another embodiment of a smart VHC. [Figure 25] 1 is a diagram showing MDI recognition via sound. [Figure 26] FIG. 10 is a graph showing amplitude versus time at various flow rates. [Figure 27] 1 is a diagram illustrating various controller inputs. [Figure 28] 1 is a flow diagram illustrating MDI usage and feedback loops. [Figure 29] FIG. 1 is a side view illustrating the use of one embodiment of a medication delivery system. [Figure 30] FIG. 10 is a perspective view of an alternative embodiment of a mask with contact sensors. [Figure 31] 1 is a schematic diagram of a mask and an enlarged cross-sectional view of a portion of the mask sealing edge. [Figure 32] 1 is a schematic diagram showing inputs / outputs for a controller. [Figure 33] 1 is a flow diagram illustrating the use of a mask. [Figure 34] 10 is a flow diagram illustrating the use of active valves. [Figure 35]1 is a cross-sectional view of one embodiment of an active valve in a flow channel of a medication delivery system. [Figure 36] FIG. 36 is an end view of one embodiment of the valve shown in FIG. 35. [Figure 37] FIG. 10 is a graph of flow versus time illustrating inhalation and exhalation cycles with and without an active valve. [Figure 38] FIG. 10 is a side view of an alternative embodiment of the smart VHC. [Figure 39] FIG. 1 shows minimum plume temperature as a function of distance from the thermocouple for various MDI products. [Figure 40] FIG. 1 is a partial cross-sectional side view of an MDI utilized in one embodiment of a VHC. [Figure 41] FIG. 1 is a partial cross-sectional side view of an MDI utilized in another embodiment of a VHC. [Figure 42] FIG. 1 is a graph illustrating force versus displacement for an exemplary MDI actuation. [Figure 43] FIG. 1 is an end view of one embodiment of a backpiece of a VHC. [Figure 44] FIG. 44 is a side view of the backpiece shown in FIG. 43. [Figure 45A] FIG. 1 is a partial cross-sectional side view of an MDI in an activated position relative to a smart VHC. [Figure 45B] FIG. 1 is a partial cross-sectional side view of an MDI in an inactivated position relative to a smart VHC. [Figure 46] FIG. 1 is a partial cross-sectional view of one embodiment of a smart MDI. [Figure 47] FIG. 1 is a partial cross-sectional view of an embodiment of a smart MDI. [Figure 48] FIG. 1 is a partial cross-sectional view of one embodiment of a smart MDI. [Figure 49] FIG. 1 is a side view of one embodiment of a smart MDI. [Figure 50] FIG. 50 is an enlarged partial view of the smart MDI shown in FIG. 49. [Figure 51A] FIG. 10 is a side view of a VHC according to an alternative embodiment. [Figure 51B]FIG. 10 is another side view of the VHC according to an alternative embodiment. [Figure 51C] FIG. 10 is another side view of the VHC according to an alternative embodiment. [Figure 52] FIG. 1 is a partial cross-sectional side view of one embodiment of a VHC. [Figure 53] FIG. 1 is a partial cross-sectional side view of one embodiment of a VHC. [Figure 54] FIG. 1 is a partial cross-sectional side view of one embodiment of a VHC. [Figure 55] FIG. 1 is a graph showing the relationship between pressure and flow rate for various MDI devices. [Figure 56] FIG. 1 is a side view of one embodiment of a VHC. [Figure 57] FIG. 57 is an enlarged, partial side view of the VHC shown in FIG. 56. [Figure 58] FIG. 1 is a side view of one embodiment of a VHC. [Figure 59A] FIG. 1 is a diagram of a duckbill valve with a vibrating beam. [Figure 59B] FIG. 10 is another view of a duckbill valve with a vibrating beam. [Figure 59C] FIG. 10 is another view of a duckbill valve with a vibrating beam. [Figure 60] FIG. 1 is a partial cross-sectional side view of an embodiment of a flow sensor assembly. [Figure 61] FIG. 1 is a partial cross-sectional side view of an embodiment of a flow sensor assembly. [Figure 62] FIG. 1 is a partial cross-sectional side view of an embodiment of a flow sensor assembly. [Figure 63] FIG. 1 is a side view of one embodiment of a VHC. [Figure 64] FIG. 10 is a side view of another embodiment of a VHC. [Figure 65] FIG. 10 is a side view of another embodiment of a VHC. [Figure 66A] FIG. 1 illustrates a graphical display with user indicators. [Figure 66B] FIG. 10 illustrates another graphical display with user indicators. [Figure 66C]FIG. 10 illustrates another graphical display with user indicators. [Figure 67] FIG. 1 is a pictorial diagram illustrating communication between a smart VHC and a user interface. [Figure 68] FIG. 1 is a partial cross-sectional side view of an MDI inserted into a VHC. [Figure 69] 1A-1C are partial cross-sectional side views of the VHC in a partially inserted position and a fully inserted position. [Figure 70] FIG. 1 is an end view of one embodiment of a VHC. [Figure 71] FIG. 10 is an end view of another embodiment of a VHC. [Figure 72] FIG. 10 is an end view of another embodiment of a VHC. [Figure 73] FIG. 10 is an end view of another embodiment of a VHC. [Figure 74] FIG. 10 is an end view of another embodiment of a VHC. [Figure 75] FIG. 1 shows an MDI with conductive material to close the circuit path within the VHC. [Figure 76] FIG. 1 is a side view of an MDI and a VHC. [Figure 77] FIG. 1 is a diagram of the display of an MDI or VHC. [Figure 78] FIG. 1 is a side view of one embodiment of a smart VHC. [Figure 79] FIG. 1 is a perspective view of a valve holding chamber with an adapter having a display. [Figure 80] FIG. 80 is a perspective view of the adapter shown in FIG. 79. [Figure 81] FIG. 1 is a perspective view of a valve holding chamber with a back piece having a display. [Figure 82] FIG. 82 is a perspective view of the back piece shown in FIG. 81. [Figure 83] 1 is a schematic diagram showing a computer structure. [Figure 84] 1 is a schematic diagram of a communication system. [Figure 85] 1 is a flow diagram illustrating a protocol for using a smart VHC and MDI. [Figure 86]FIG. 1 is a diagram of a smart VHC and MDI. [Figure 87] FIG. 1 is a side view of an embodiment of an active valve. DETAILED DESCRIPTION OF THE INVENTION

[0013] The term "plurality," as used herein, should be understood to mean two or more. The term "coupled" means, for example, connected or engaged with an intervening member, whether directly or indirectly; such term does not require a fixed or permanent engagement, although it may be fixed or permanent (or integral), and includes both mechanical and electrical connections. Terms such as "first," "second," and the like, as used herein, are not meant to be assigned to the particular component so designated, but rather simply refer to such components in the designated numerical order, meaning that a component designated as a "first" may later be a "second" such component, depending on the order in which it is mentioned. Furthermore, the designations "first" and "second" do not necessarily mean that the two components or values ​​so designated are different from one another; for example, a first component may be the same as a second component, and each may simply refer to a separate but identical component.

[0014] In the traditional patient / prescriber / payer model, a patient is prescribed a treatment and the patient purchases the drug and / or treatment device. When the purchase is covered by the payer, there is typically no feedback to the payer that the treatment was performed correctly and as prescribed, apart from future requirements for additional treatment. The patient is typically trained in using the medical device by the prescriber and then required to use the device in their daily life. At some point, the patient may follow the prescriber for a change in condition, a re-prescription, or perhaps at a set frequency. At such time, the prescriber evaluates the effectiveness of the treatment and decides to modify or continue the treatment. If the prescriber decides to modify the treatment, a new prescription is given and the cycle repeats. Some of the technical challenges faced in improving adherence to treatment regimens that can result in improved cost tracking and diagnostics include challenges in the ability to effectively monitor the functionality and usage of different treatment devices, how to provide effective real-time feedback to the user and / or prescriber, and how to make real-time changes to the user's device and device performance and / or user behavior / technique in a particular instance.

[0015] 1 and 2, various smart devices and associated feedback can be implemented to improve the effectiveness of treatment. Additionally, prescribers are provided with patient-specific data to make informed decisions regarding treatment, including the medication, and payers are provided with assurance that patients have adhered to a treatment regimen before covering the cost of another prescription.

[0016] Referring to FIG. 3 , one exemplary embodiment of a smart VHC includes a chamber housing 2 having walls defining an interior space 4 extending along a longitudinal axis / inhalation flow path 6, a backpiece 8 coupled to an input end 10 of the chamber housing, and a mouthpiece and / or valve assembly 12 coupled to an output end 14 of the chamber housing. The mouthpiece assembly may be releasably and detachably coupled to the chamber housing, e.g., with tabs received in grooves. The mouthpiece includes an inhalation valve 16 and / or an exhalation valve 18, with the exhalation valve providing the exhalation flow path 13. The inhalation and exhalation valves may alternatively be provided on other components of the VHC. In various embodiments, the valves are configured as part of an annular toroidal valve having an inner periphery that defines the inhalation valve 16 and an outer periphery that defines the exhalation valve 18. In other embodiments, the inhalation valve is configured as a duckbill valve, which may further include an outer annular flange that defines the exhalation valve. In other embodiments, the inhalation and exhalation valves may not be integral, but instead may be separately formed and disposed within the VHC. The backpiece 8 includes an opening 20 shaped to receive a mouthpiece portion 22 of an MDI actuation boot 24. The boot further includes a chimney portion 26 having a cavity shaped to receive a medication container 28. The boot further includes a support block having a well shaped to receive a valve stem of an MDI. The well communicates with an orifice that releases aerosolized medication into the interior space of the chamber housing. Various embodiments of VHCs and MDIs, including mouthpiece assemblies, chamber housings, and backpieces, are disclosed, for example and without limitation, in U.S. Patent Nos. 6,557,549, 7,201,165, 7,360,537, and 8,550,067, all of which are assigned to the assignee of the present application, Trudell Medical International, and are hereby incorporated by reference in their entireties.

[0017] In one embodiment, the VHC 3 is configured to accurately identify an MDI inserted into the VHC, accurately identify when an MDI 5 is activated, and monitor proper technique and provide feedback to the user regarding proper technique, as shown, for example, in FIG. 12. For example, with reference to FIGS. 3 and 7, the VHC can include a blue LED 30 coupled to a wall of the chamber housing within the interior space 4 and a photodetector 32 disposed within the interior space 4 at a location spaced from the LED 30. The photodetector 32 can be coupled to the wall, for example. A camera 35 can be coupled to the holding chamber 2, for example, adjacent the mouthpiece assembly 12 or near the backpiece 8. A flow detector, for example, a flow sensor 34, is coupled to the wall of the chamber housing, the flow sensor having an inlet port 36 and an outlet port 38 in communication with the interior space. A feedback device, for example, a visual feedback indicator 40, for example, an LED or an array of LEDs, is provided on the backpiece 8, although it may also be coupled to the chamber housing or the mouthpiece assembly.

[0018] As shown in FIGS. 79 and 80 , the adapter 50 includes a shell having a C-shaped interior 52 configured to engage the chamber housing 2, e.g., by a snap fit. The adapter has a feedback device configured as a display 54 visible to the user, and such adapters may include a microcontroller 56 and communication components. As shown in FIGS. 81 and 82 , the backpiece includes the display 54 and / or microcontroller 56. The display 54 in each embodiment displays various information to the user and / or caregiver, such as various feedback information disclosed herein. In various embodiments, the microcontroller 56 may be embodied as the controller configuration shown in FIG. 16 , as the microcontroller configuration of FIG. 22 or FIG. 27 , or as a processor 502 with one or more components of a more complete computer 500, as shown in FIG. 83 .

[0019] Communications and Data Processing To meet these challenges, a device, such as a VHC associated with an MDI, may be configured to do one or more of the following: (1) accurately identify the MDI being used with the VHC; (2) accurately identify when the MDI is activated; (3) monitor proper technique and provide feedback to the user regarding this technique; and (4) provide patient-specific data to the prescriber and / or provider. With reference to Figures 2, 16, 65, 66A-66C, 67, 83, and 84, one aspect of these embodiments relates to data handling. Data logged by the VHC and / or MDI may be transmitted to an external device, such as a smartphone, tablet, or personal computer. If such an external device is unavailable, the data may be stored internally within the VHC and / or MDI in a data storage module or other storage device and transmitted upon the next synchronization of the VHC / MDI with the external device. Software may accompany the VHC / MDI to perform data transmission and analysis.

[0020] To enable rapid and accurate processing of data generated within the smart VHC and / or MDI, for example from one or more various sensors, the data may be wirelessly communicated to a smartphone, a local computing device, and / or a remote computing device, which may interpret and act on the raw sensor data.

[0021] In one embodiment, the smart VHC and / or MDI includes circuitry that transmits raw sensor data in real time to a local device, such as a smartphone. The smartphone may display graphics or instructions to the user and may execute processing software to interpret and act on the raw data. The smartphone may include software that filters and processes the raw sensor data and outputs relevant status information contained in the raw sensor data to a display on the smartphone. The smartphone or other local computing device may alternatively use its local resources to contact a remote database or server to retrieve processing instructions or to route raw sensor data for remote processing or interpretation, and to receive processed and interpreted sensor data back from the remote server for display to the user or a caregiver accompanying the user of the smart VHC.

[0022] In addition to simply providing data, statistics, or instructions on the display of a smartphone or other local computer located near the smart VHC and / or MDI, the smart VHC and / or MDI can actively manage and control proactive operations related to the smart VHC and / or MDI. For example, if the smartphone or other local computer located near the smart VHC and / or MDI determines that sensor data indicates the end of treatment has been reached or that another treatment is required, the smartphone or other local computing device can communicate such information directly to the patient. Other variations are also contemplated; for example, a remote server in communication with the smartphone or in direct communication with the smart VHC and / or MDI via a communications network can provide information and instructions to the patient / user.

[0023] In yet another embodiment, real-time data collected at the smart VHC and / or MDI and relayed to a remote server via a smartphone can trigger the remote server to locate and notify a physician or managing caregiver regarding issues with a particular treatment session or patterns developed over time based on past treatment sessions for a particular user. Based on data from one or more sensors in the smart VHC and / or MDI, the remote server generates alerts and sends them to the user, the user's physician or other caregiver via text, email, or other electronic communication medium.

[0024] The electronic circuitry within the smart VHC and / or MDI (e.g., the controller configuration of FIG. 16), the local computing device and / or the remote server described above may include some or all of the functionality of computer 500, which is in direct communication with network 526 and / or other computers. As shown in FIGS. 65, 66A-66C, 67, 76, 77, 83, and 84, computer 500 may have a processor 502, a memory device 516, a display or other output device 510, an input device 512, and a network interface device 520, all of which are connected to each other via bus 508. A battery 503 is coupled to the computer to power the computer. The computer may communicate with a network. Processor 502 represents a central processing unit of any type of architecture, such as CISC (Complex Instruction Set Computing), RISC (Reduced Instruction Set Computing), VLIW (Very Long Instruction Word), or hybrid architecture, although any suitable processor may be used. Processor 502 executes instructions and includes the portion of computer 500 that controls the operation of the entire computer. Although not shown in FIGS. 83 and 84, processor 502 typically includes a control unit that organizes data and program storage areas in memory and transfers data and other information between various portions of computer 500. Processor 502 receives input data from input device 512, and network 526 reads and stores instructions (e.g., processor executable code) 524 and data in main memory 504, e.g., random access memory (RAM), static memory 506, e.g., read-only memory (ROM), and memory 516. The processor 502 may provide data to a user via an output device 510 .

[0025] Although computer 500 is shown as including only a single processor 502 and a single bus 508, the disclosed embodiments apply equally to computers that may have multiple processors and multiple buses, some or all of which perform different functions in different ways.

[0026] Storage device 516 represents one or more mechanisms for storing data. For example, storage device 516 may include computer-readable media 522, such as read-only memory (ROM), RAM, non-volatile storage media, optical storage media, flash memory devices, and / or other machine-readable media. In other embodiments, any suitable type of storage device may be used. While only one storage device 516 is shown, multiple storage devices and multiple types of storage devices may be present. Furthermore, while computer 500 is depicted as having storage device 516, computer 500 may be distributed across other computers, such as on a server.

[0027] The storage device 516 may include a computer-readable medium 522 containing instructions 524 executable on the processor 502 to perform the functions described above in connection with the controller (not shown) and processing of sensor data, display sensor data or instructions based on the sensor data, control aspects of the smart VHC and / or MDI to change its operation, or contact third parties or other remotely located resources to provide update information to or retrieve data from such remotely located resources. In another embodiment, some or all of the functions are implemented by hardware instead of a processor-based system. In one embodiment, the controller is a web browser, but in other embodiments, the controller may be a database system, file system, email system, media manager, image manager, or any other facility capable of accessing data items. The storage device 516 may also include additional software and data (not shown) that are not necessary to understanding the present invention.

[0028] Output device 510 is the portion of computer 500 that displays output to a user. Output device 510 may be a liquid crystal display (LCD), which is well known in the computer hardware art. In other embodiments, output device 510 may be replaced by a gas or plasma-based flat panel display or a traditional cathode ray tube (CRT) display. In still other embodiments, any suitable display device may be used. Although only one output device 510 is shown, in other embodiments, any number of output devices, of different or the same type, may be present. In one embodiment, output device 510 displays a user interface. Input device 512 may be a keyboard, a mouse or other pointing device, a trackball, a touchpad, a touchscreen, a keypad, a microphone, a voice recognition device, or any other suitable mechanism for a user to input data into computer 500 and operate the user interface described above. Although only one input device 512 is shown, in other embodiments, any number and type of input devices may be present.

[0029] The network interface device 520 provides connectivity from the computer 500 to a network 526 via any suitable communication protocol. The network interface device 520 sends and receives data items to and from the network 526 via a wireless or wired transceiver 514. The transceiver 514 may be cellular frequency, radio frequency (RF), infrared (IR), or any of a number of known wireless or wired transmission systems capable of communicating with the network 526 or other smart devices 102 having some or all of the features of the example computers of FIGS. 83 and 84. The bus 508 may represent one or more buses, such as USB, PCI, ISA (Industry Standard Architecture), X-Bus, EISA (Extended Industry Standard Architecture), or any other suitable bus and / or bridge (also called a bus controller).

[0030] Computer 500 may be implemented using any suitable hardware and / or software, such as a personal computer or other electronic computing device. Computer 500 may be a portable computer, laptop, tablet, or notebook computer, a smartphone, a PDA, a pocket computer, an appliance, a telephone, or a mainframe computer are examples of other possible forms of computer 500. Network 526 may be any suitable network, and network 526 may support any suitable protocol suitable for communication to computer 500. In one embodiment, network 526 may support wireless communication. In another embodiment, network 526 may support hardwired communication, such as telephone lines or cables. In another embodiment, network 526 may support the Ethernet IEEE (Institute of Electrical and Electronics Engineers) 802.3x specification. In another embodiment, network 526 may be the Internet, and such a network may support IP (Internet Protocol). In another embodiment, network 526 may be a LAN or WAN. In another embodiment, network 526 may be a hotspot service provider network. In another embodiment, network 526 may be an intranet. In another embodiment, network 526 may be a General Packet Radio Service (GPRS) network. In another embodiment, network 526 may be any suitable cellular data network or cell-based wireless network technology. In another embodiment, network 526 may be an IEEE 802.11 wireless network. In yet another embodiment, network 526 may be any suitable network or combination of networks.Although one network 526 is shown, in other embodiments, any number of networks (of the same type or of different types) may be present.

[0031] It should be understood that the various techniques described herein can be implemented in connection with hardware or software, or a combination of both, where applicable. Thus, the methods and apparatus of the present invention disclosed herein, or certain aspects or portions thereof, may be in the form of program code (i.e., instructions) embodied in a tangible medium, such as a floppy disk, CD-ROM, hard drive, or any other machine-readable storage medium, such that when the program code is loaded into and executed by a machine, e.g., a computer, the machine becomes an apparatus for implementing the invention disclosed herein. In the case of program code execution on a programmable computer, the computing device generally includes a processor, a processor-readable storage medium (including volatile and nonvolatile memory and / or storage elements), at least one input device, and at least one output device. One or more programs may embody or use the processes described in connection with the invention disclosed herein, for example, through the use of an API, reusable controller, etc. Such programs may be implemented in a high-level procedural or object-oriented programming language to communicate with a computer system. However, the programs may also be implemented in assembly or machine language, if desired. In either case, the language may be a compiled or interpreted language, and the language may be combined with hardware implementations. While example embodiments may refer to use of the inventive aspects disclosed herein in connection with one or more standalone computer systems, the invention is not so limited and may instead be embodied in connection with any computing environment, such as a networked or distributed computing environment. Furthermore, the inventive aspects disclosed herein may be embodied within or across multiple processing chips, and storage may similarly be spread across multiple devices. Such devices may include, for example, personal computers, network servers, and handheld devices.

[0032] Appropriate Technology Providing feedback to the user regarding their breathing technique is a feature of the VHC that helps optimize drug delivery. In one embodiment, shown in FIGS. 3 and 9, a flow detector configured as a flow sensor 34 is used to collect data and provide technique feedback. The flow sensor measures the flow rate at which the user is inhaling. Inhaling too quickly can deposit most of the medication in the throat rather than in the lungs. Effective drug deposition in the lungs can be achieved by controlled inhalation. Additionally, the flow rate can be integrated over time to determine the amount of air inhaled, which can be used to provide the user with an indication of when they have emptied the interior space of the chamber housing and received the entire dose. As shown in FIGS. 3 and 9, the flow sensor 34 has a bypass channel 58 with an input port 36 and an output port 38 communicating with the interior space. The pressure difference between the proximal and distal openings defined by the input and output ports causes a small flow rate through the bypass channel. A thermal mass airflow sensor 60 is used to measure the flow rate through the bypass channel, which is correlated to inspiration flow rate as shown in FIG. 9. Flow sensors 34, 34' may be located at the respective locations shown in FIG. 9. The flow sensors measure the flow rate through the flow path within interior space 4 without being positioned within or obstructing such a flow path. Thus, the flow path sensor does not interfere with the aerosolized medication or the flow path through the interior space. Combining flow rate information with MDI actuation detection and MDI discrimination, described in more detail below, can provide reliable insight into patient behavior and device use.

[0033] Referring to FIG. 12 , flow information can be used in real time to provide the user, for example, via a feedback device, such as an indicator (visual, auditory, and / or tactile) or display, with feedback regarding the clinical session and whether the user should begin inhalation and / or whether the user needs to slow the flow rate, for example, if the maximum flow rate is exceeded. MDI actuation can also be used to provide the user with feedback regarding the initiation of actuation and / or the beginning of inspiration. First, the user 66 inserts the MDI into the backpiece as shown in FIG. 19 . A contact switch 62 or other MDI insertion detector or sensor detects this insertion. Upon insertion of the MDI, the smart VHC actively seeks MDI actuation and / or inspiration flow detection. In response to feedback from the feedback device (e.g., an indicator or display), the user can actuate the MDI, thereby dispensing aerosolized medication into the interior space, with the actuation timestamp recorded. The processor 502 then seeks the inspiration flow rate reported by the flow sensor 34 and records the flow rate and the timestamp of the active inspiration. The processor 502 also compares the inhalation flow rate with a stored predetermined flow rate, e.g., a maximum recommended flow rate, and provides feedback to the user if the inhalation flow rate exceeds the predetermined flow rate. The processor then compares the inhalation volume calculated from the flow rate with the volume of the internal space 4 and notifies the user that the treatment or procedure is complete and the dose has been properly administered. Alternatively, the processor can further inform the user that a breath is required to completely empty the internal space. It is noted that the user has the option to train with the device before beginning treatment. In this case, no MDI is inserted. Alternatively, only the flow sensor is activated. The processor records the flow rate, provides feedback regarding the flow rate, and notifies the user that training is complete.

[0034] 14-17, one embodiment of a smart VHC includes a thin-skin patch having resistive strain gauges 68 attached to the inhalation valve 16 to measure the geometry of the valve opening 70 during inspiration. The strain gauges may be attached to the valve by adhesive or by insert molding during the valve's injection molding. As shown in FIG. 15, the size and opening duration of the valve 16 opening can be correlated with inspiration flow to confirm completion of rest.

[0035] As shown in FIG. 16 , a controller, which can be located on or within various embodiments of a smart VHC described herein, is in communication with one or more sensors, switches, and / or meters that track or control the operation of the smart VHC. The controller can store collected data in memory for later download to a receiving device or transmit data to a receiving device in real time. Additionally, the controller can perform some processing of the collected data from the sensors or store or transmit raw data. An RF transmitter or receiver module can be associated with the controller provided in the smart VHC, thereby communicating with a remote handheld or fixed computing device in real time or at a later time when the smart VHC is within communication range of a communications network for the remote handheld or fixed computing device. The controller can have one or more of the features of the computer system 500 shown in FIG. 83 . Additionally, one or more sensors, switches, or meters can be in wired or wireless communication with the controller.

[0036] For clarity, controller circuitry is omitted when displaying other features of the various described smart VHC embodiments; however, a controller or other processing agent capable of at least managing the transmission or storage of data from the smart VHC is envisioned in some of these embodiments. In other embodiments, the smart VHC may not include an on-board processor, and the various sensors, meters, and switches of certain embodiments may communicate directly and wirelessly with a remotely located controller or other processing device, such as a handheld device or a remote server. Data collected by the controller or other processing device can be compared to expected or preprogrammed values ​​in local controller memory or other remote locations to provide feedback on whether desired performance or both is occurring. If the controller is more sophisticated and includes many of the elements of the computer 500 described in FIG. 83, this processing may be entirely local to the smart device (smart VHC, smart MDI, etc.). In more rudimentary controller configurations, data may simply be date / time-stamped and stored locally or remotely for later processing. In one embodiment, data may also be displayed locally or remotely by a unique device or patient identifier.

[0037] Breath holding is also a specific step to facilitate drug diffusion and optimize deposition in the lungs. A user's breath holding can be monitored using the methods described below, or the user may simply be prompted visually or acoustically to hold their breath without directly monitoring breath holding.

[0038] 1. Carbon dioxide detection 1.1. Referring to FIG. 86, carbon dioxide is a by-product of cellular respiration that is expelled from the body through exhalation. As a result, the concentration of carbon dioxide during exhalation is significantly higher than that in ambient air. A carbon dioxide sensor 76 can be used to monitor carbon dioxide concentration within the mouthpiece and mask adapter portion of the VHC, with higher concentrations indicative of the exhalation phase of the user's breathing cycle. This data, combined with inspiratory flow or other means of detecting the user's inhalation, can be used to calculate breath-hold duration and provide feedback to the user. The end of inspiration can be identified, for example, using a flow or pressure threshold. Once inspiratory flow or pressure falls below this threshold, a breath-hold timer is started that will not stop until a spike in carbon dioxide concentration is detected.

[0039] 2. Pressure monitoring 2.1. Referring to Figures 18-20, a pressure sensor 78 may be positioned within the mouthpiece / mask adapter or chamber housing so that the inhalation and exhalation phases of the user's breathing cycle can be monitored. Inhalation and exhalation pressure thresholds may be used to calculate the user's breath-holding duration. If the inhalation pressure falls below the inhalation threshold, a breath-holding timer is started, and once exhalation begins and exceeds the exhalation pressure threshold, the breath-holding timer is stopped. The pressure sensor 78 is in communication with the computer 500 and the processor 502.

[0040] Additionally, the device provides information about when the chamber is empty by counting the number of inspirations based on an assumed tidal volume. The assumed tidal volume is based on age and gender and can be selected during setup. Since the volume of the interior space 4 is known, the computer 500 / processor 502 processes positive pressure events to identify when the MDI is actuated, then counts the number of negative pressure events indicating inspiration until the chamber volume is reached. Each negative pressure event should be spaced apart by a normal breathing cycle, e.g., 2-5 seconds, and the chamber volume is evacuated within a finite total treatment period. If this is met, a determination is made that medication has been fully delivered. If not, feedback can be provided to the user to continue the inspiration and / or breathing cycle. Feedback can be audible, visual, or tactile / kinesthetic (e.g., vibration), using various indicators described elsewhere herein, or any combination thereof. Information can be logged and stored, and / or feedback can be provided that further training is required.

[0041] 3. Microphone 3.1 In use, inhaled and exhaled air travels different paths through the VHC. Because different flow paths are used, the flow through these paths can produce different sounds. For example, microphone 82 shown in FIG. 24 can be used to listen to inhalations and exhalations, and this microphone can be used to calculate breath-hold duration using a threshold method similar to Examples 1.1 and 2.1.

[0042] Additionally, during treatment, once the MDI is activated, a microphone records the sound of the airflow through the VHC, and this sound can be monitored and analyzed by a microprocessor based on the amount of turbulence recorded by the microphone. For example, the loudness of the sound recorded over a period of time can be correlated with a particular flow rate or range of flow rates, as shown in FIG. 26. The VHC can provide feedback to the user via indicators (visual, audible, tactile, etc.) that the inspiratory volume is excessive or exceeds a predetermined maximum flow rate. Other feedback can include that the treatment or procedure is complete or that data upload is complete. Upon completion of treatment, the system resets and is ready for another MDI activation.

[0043] Referring to FIG. 58, a reed or array or series of reeds 84, e.g., plastic or silicone, can be placed adjacent to a microphone 82. Differences in flow rate excite or produce different acoustic outputs from the reeds, which can be picked up and recorded by the microphone 82. As shown in FIGS. 59A-59C, a single reed 115 or beam can be placed across the mouth of a valve, shown as a duckbill valve. Acting as a vibrating string, the reed 115 is made thin or thick as the valve flaps 88 open and close by different amounts, e.g., in response to flow rate, so that the reeds produce different acoustic signals that can be picked up by the microphone 82. The microphone is in communication with a computer 500 and a processor 502.

[0044] 4. Humidity sensor 4.1. Air from the ambient environment becomes saturated with water vapor when it enters the lungs. When this air is exhaled, it passes through the mouthpiece and mask adapter where the humidity of the air can be analyzed. By continuously monitoring the humidity level with a sensor 90 shown in FIG. 86 in the mouthpiece and mask adapter, the exhalation phase of the breathing cycle can be detected and used to determine breath-hold duration in the same manner as in embodiments 1.1 and 2.1. The humidity sensor 90 is in communication with the computer 500 and the processor 502.

[0045] 5. Temperature Sensor 5.1. As ambient air enters the body, it warms to body temperature. Using a temperature sensor 92 (see, e.g., FIG. 86), the air temperature can be monitored in the mouthpiece and mask adapter. If a sudden increase in temperature is observed, this can be interpreted as an exhalation from the user. As with the previous breath-holding detection embodiment, this detection of the start of exhalation can be combined with an inhalation measurement (i.e., flow or pressure) to calculate breath-holding duration and provide feedback to the user, thereby improving their technique. The temperature sensor 92 is in communication with the computer 500 and processor 502.

[0046] 6. Light Curtain 6.1. Referring to FIGS. 63 and 86, a light curtain 94 or multiple light curtains may be used with a flexible member 96 responsive to negative and positive pressure. During inspiration, the flexible member may be pulled in a direction that blocks (or restores) the light beam of one of the pair of light curtains, which may be interpreted as an inhalation by the user. In contrast, during exhalation, the flexible member may be pushed in the opposite direction, in which case the second of the light curtains blocks (or restores) its beam, which may be interpreted as an exhalation by the user. Using these measurements, the time that both light curtains are unblocked indicates the duration of the breath-hold. Alternatively, a single light curtain may be used to detect capture by the user, and other methods (e.g., inspiration pressure or flow thresholds) may be used to determine the end of inspiration.

[0047] 6.2. In another embodiment, the moisture in the user's breath may be sufficient to block the light curtain responsible for detecting the breath, in which case a flexible member is not required.

[0048] End of treatment When receiving aerosol from a valved holding chamber for mask products, particularly in infants and children, there is a known uncertainty as to when the user has received all of the medication from the holding chamber. Premature chamber removal can result in an underdose, as can excessive mask leakage during aerosol administration. Monitoring the amount of aerosol in the chamber or the amount of air being rested through the chamber can provide feedback to the user regarding the end of treatment. This provides patient health and dosage assurance for all parties involved.

[0049] 1.Capacity change 1.1. Assuming that the aerosol has a different dielectric compared to that of air, the change in capacitance of the chapatita 106 shown in Figures 43 and 44 can be used to detect when all of the aerosol has left the chamber. A baseline capacitance is measured prior to aerosol actuation, and treatment is not terminated until the capacitance returns to this baseline value or some similar value.

[0050] 2.Light transmission / reflection 2.1. As shown in Figures 3 and 7, the light source 30 and photodetector 32 can be set up in any orientation relative to the flow, with the light source pointed directly at the photodetector or reflected off a surface towards the photodetector. If aerosols are present, this light will be scattered, diffused, diffracted, absorbed, and reflected, resulting in a decrease in the amount of light returning to the photodetector. The end of treatment occurs when the baseline reading is approached.

[0051] Flow Detection Aerosol deposition in the throat and upper airways can occur if the flow rate becomes too high, leading to side effects and robbing the lungs of drug. A smart VHC should have a feedback device or feature that uses a flow detector to alert the user when a predetermined maximum recommended flow rate is exceeded and allow the user to slow their inhalation to an effective volume. As described below, any embodiment of a flow detector, alone or in combination, can be used for this purpose in addition to helping determine the end of treatment. The end of treatment is determined by integrating these flow rates over time until a threshold volume is reached, as shown in FIG. 12. The threshold volume is selected so that all aerosol is inhaled from the chamber.

[0052] 3. Pressure Sensor 3.1.Pressure difference across the valve The valve is selected so that its resistance is constant, has low hysteresis, and is preferably linear, as shown in Figure 46. The flow rate through the valve can then be estimated as a function of the pressure difference reading across the valve.

[0053] 3.2.Pressure difference before and after MDI 3.2.1.MDI Boots The MDI identifier is used to identify the MDI that is being used with the chamber. Assuming this information is known, the resistance profile (curve representing the relationship between pressure and flow rate) of the MDI can be accessed from a pre-defined database, and the flow rate through the MDI itself can be calculated using a differential pressure measurement method in which the pressure at the mouthpiece of the MDI, detected by pressure sensor 78, is compared to atmospheric pressure, as shown in Figure 47.

[0054] 3.2.2. Molded MDI Adapter Boot (Canister Insert Type) Since most MDIs have different resistance profiles, the canister can be removed from the boot and placed in a built-in container molded into the MDI adapter or backpiece. This adapter allows all MDI canisters to be inserted and still allow the aerosol to enter the chamber. In this case, the flow resistance of the MDI adapter can be specifically designed to meet the system requirements: a linear P curve, low hysteresis, and part-to-part consistency.

[0055] 3.3.Pressure difference across the bypass orifice 3, 9, 49, and 50, a bypass channel 60 resides inside the chamber wall or mouthpiece / mask adapter, and is in fluid communication with the aerosol chamber. During inspiration, some flow passes through this bypass channel and is drawn through a precisely sized orifice 110. The flow resistance of this orifice can be fully characterized, and measurements of the pressure difference across the orifice 110 using pressure sensor 78 can be used to calculate the flow rate through the orifice and bypass channel. The flow rate through the chamber is calibrated to the flow rate through the bypass channel, so that during use, the bypass flow measurement can indicate the total flow rate through the VHC. Pressure sensor 78 is in communication with computer 500 and processor 502.

[0056] 3.4.Venturi 3.4.1. The Venturi 112 uses a local restriction in the flow path to accelerate the fluid as it passes through. As the flow velocity increases, its pressure decreases relative to the pressure of the slower moving flow upstream of the restriction. A pressure differential sensor can detect this difference, and with knowledge of the Venturi geometry, the flow rate can be calculated.

[0057] The venturi 112 may be molded as part of the chamber housing 2, as part of the mouthpiece 12, or as part of the bypass flow path 60, as shown in Figures 51A-51C, respectively. The pressure sensor 78 is in communication with the computer 500 and the processor 502.

[0058] 3.5. Pitot-Static Tube 3.5.1. The Pitot-Static Tube 114 consists of a tube with one closed end and a means for comparing the pressure within the tube with the ambient fluid pressure. When rapidly moving air enters the Pitot Tube 114, it stagnates, increasing the pressure within the tube that is proportional to the initial velocity of the fluid flow.

[0059] The pitot tube may be molded into or assembled to the baffle 116 of the valved holding chamber to sample the fastest moving air during inspiration, as shown in Figure 52. This velocity can be converted into a flow rate estimate with knowledge of the chamber geometry. Pressure sensor 78 detects the pressure difference, which is in communication with computer 500 and processor 502.

[0060] 4. Sound-based method For all sound-based methods, a second microphone can be used to detect ambient noise. This information can then be used for noise reduction in signals being processed by the microcontroller or other processor 502.

[0061] 4.1.Volume usage type 4.1.1. Specific sounds As air rushes through the MDI and valved holding chamber, turbulence is created, which produces sound. At high flow rates, there is a lot of turbulence and a lot of sound. Monitoring the loudness of the sound in the chamber can provide a means of estimating flow rate, however, unfiltered, volume-based methods are highly susceptible to environmental noise.

[0062] A microphone 82 is located within the interior space of the chamber housing, such as coupled to an adapter or backpiece (see, e.g., FIG. 24), or along the chamber or at the baffle (see, e.g., FIG. 59C). This same microphone can be used for MDI actuation detection.

[0063] 4.1.2.Sound Generation A microphone is placed in approximately the same spot as in embodiment 4.1.1. As shown in Figure 58 and Figures 59A and 59B, a vibrating reed 115 or multiple reeds 84, edge sounds, or flow over an open or closed tube can be used to create a sound as the flow passes by, which should be substantially louder than the volume present within the chamber itself. The microphone 82 is in communication with a computer 500 and a processor 502.

[0064] 4.2. Low-pass, high-pass and band-pass filters using volume As mentioned in embodiment 4.1.1, volume-based methods can be prone to false readings due to ambient noise. To reduce this risk, digital and / or analog filtering processes are implemented to ensure that the system effectively "listens" to only specific frequency bands. These filters are selected to listen for sounds specific to the chamber or monitor these frequencies in the event of sound generation.

[0065] 4.3. Algorithm-based The sounds coming from the chamber at different flow rates are quite system specific, whether these sounds are inherent to the product or are produced by reeds or other sound sources. Various algorithms can be used to quantitatively compare the incoming microphone signals to pre-recorded signal ranges at defined flow rates from within the device.

[0066] 4.4. Time of Flight (TOF) Referring to FIG. 64, acoustic TOF, in this case, refers to the time it takes for sound to travel from one acoustic transceiver 118 to another. Transceiver 1 (T1) is located downstream of transceiver 2 (T2), both of which may be located inside or outside the chamber. When sound travels from T1 to T2, it is effectively slowed down as a result of traveling against the airflow through the chamber. Conversely, when sound travels from T2 to T1, it is faster than normal because it moves with the flow. Knowing the angle θ of the transceiver 118 or ultrasonic transducer relative to the flow direction and the TOF from T1 to T2 and from T2 to T1, the average flow velocity and thus the flow rate can be estimated with knowledge of the chamber geometry. Sound of any frequency can be useful, but it is desirable for it to be outside the range of human hearing (above 20 kHz). The transceiver 118 communicates with the computer 500 and the processor 502.

[0067] Doppler Doppler ultrasound uses the change in frequency of reflected waves relative to transmitted waves to estimate the speed at which a reflector is moving. When suspended aerosol particles are used as reflectors, the Doppler principle can be used to determine the average particle velocity and thus estimate flow rate. This method only detects flow when aerosols are present, and therefore can also be used as another dosage assurance tool.

[0068] 53, the ultrasonic transducer 118 can be located within the baffle 116 with the sound directed towards the MDI adapter or backpiece 8, within the MDI adapter with the sound directed towards the baffle, or anywhere in between as long as the sound generation is not perpendicular to the direction of airflow. The transceiver / transducer 118 is in communication with a computer 500 and a processor 502.

[0069] 5.How to use light 5.1. Internal reflection within the slit valve Referring to Figure 60, a light emitting diode (LED) 122 or other light source and / or photodetector 124 sensitive to the wavelength of light from the LED is positioned within the valve 16, both of which are directed toward a valve opening 126. The valve is of the type with a variable size opening whose opening size is determined by the flow rate through the valve. Duckbill valves, cross valves, and any die-cut valves are good examples, although this list is not exhaustive. Referring to Figures 56 and 57, the photodetector 124 may be positioned external to the valve.

[0070] During operation, a light source illuminates the inside / backside of the valve 16, which reflects a percentage of this light back to the photodetector as shown in FIG. 60 or passes the light to be received by the photodetector as disclosed in FIGS. 56 and 57. When the valve is closed, most of the light from the source is reflected back to the photodetector (inside) or not received by the photodetector (outside). When the valve is open, a larger portion of this light is allowed to escape, resulting in less light being reflected back to the photodetector (inside) or conversely, less light being received by the photodetector (outside). By monitoring the signal from the photodetector, the degree of valve opening can be estimated, along with the flow through the valve. The valve can be designed in a way that uses shape and color to focus the reflected light onto the photodetector for a particular degree of valve opening. The photodetector 124 is in communication with the computer 500 and the processor 502.

[0071] A physical shield may be positioned within the valve. The LED may have adjustable brightness so that during an initial calibration phase, the same baseline signal is achieved by iteratively increasing the LED's brightness with feedback from the photodetector or by selecting a wavelength of light that is not readily absorbed by the drug being used. Any wavelength may be used in this method, but wavelengths that are minimally absorbed or reflected by aerosols are preferred. A high-pass filter may also be implemented to remove any signal contributions from DC power sources (flashlights, sunlight) and low-frequency electric lighting, e.g., 60 Hz (120 Hz) lights in North America and equivalent frequencies worldwide.

[0072] Alternatively or in addition to broadband filtering, the intensity of the light source can be varied at a specific frequency, and a frequency detection algorithm can be used to analyze this signal for flow, where the magnitude of frequency components in the signal matched to the light source frequency will decrease or increase as the valve opens or closes, respectively.

[0073] 5.2. Shining from inside the slit valve 5.2.1.External light source Referring to Figure 61, a light source 122 is positioned outside and directed toward the valve 16 of the type in the embodiment described in Section 5.1, and a photodetector 124 remains positioned inside the valve facing the light source. In this embodiment, the more the valve opens the opening 126, the more light reaches the photodetector. Similar methods are available for this embodiment as described in Section 5.1, including filtering and frequency encoding and some of 5.1's susceptibility to drug interference. The photodetector 124 is in communication with a computer 500 and a processor 502.

[0074] 5.2.2. Body heat (infrared rays) Similar to the embodiments described in Sections 5.1 and 5.2, and referring to FIG. 62, an infrared photodetector 128 is positioned inside a valve 16 of the type described in Sections 5.1 and 5.2. As in Section 5.2, when the valve 16 is open, a large amount of light reaches the photodetector 128. In this embodiment, the photodetector is selected so that it is most sensitive to infrared wavelengths emitted by the human body. When the infrared-opaque valve is open, a large amount of infrared light emitted from the user's mouth (mouthpiece device) or face (mask device) enters and is absorbed by the photodetector or photodiode. The photodetector 128 is in communication with a computer 500 and a processor 502. This signal is analyzed by a microcontroller.

[0075] 5.3. Vibration body Referring to FIG. 63, the light source 122 and the light detector 124 face each other with the opaque body 96 positioned therebetween.

[0076] The opaque body is free to move so that it can block light from the source from reaching the detector at position 1 and the opaque body allows light to reach the detector at position 2.

[0077] The opaque body is designed to vibrate in the presence of flow, with the vibrations characteristic of different flow rates. The amplitude of these vibrations is such that positions 1 and 2 are reached. The vibrating body may be a reed made of silicone or plastic, a moving vane, a rotating vane, or a flapping piece of loose or rigid material similar to the flapping piece of a flag. This is not exclusive, as any vibrating object will work. The signal from the photodetector is then continuously analyzed, and the corresponding flow rate is estimated. The photodetector 124 is in communication with the computer 500 and the processor 502.

[0078] 6. Spring Displacement The following embodiments utilize the movement of a spring (linear or non-linear, tension or compression) that responds to either inspiration pressure or inspiration flow. As the spring moves from one position to another, it carries or activates a range of detection hardware with it, as follows:

[0079] 6.1.Hall effect A magnet is positioned at the movable end of the spring, and a Hall Effect sensor is located at a fixed position. The Hall Effect sensor detects changes in the magnetic field as the magnet moves from one position to another and analyzes this using various algorithms to determine the flow rate.

[0080] 6.2.Capacitance A charged plate is positioned on the movable end of the spring, and an oppositely charged plate is placed in a fixed position, separated by air (a dielectric). As the charged plate on the spring moves, capacitance changes, which can be detected using various hardware and software methods.

[0081] 6.3.Reed Switch A magnet is positioned on the movable end of the spring and collection or magnetic reed switches are positioned along the length of the spring. As the spring flexes, carrying the magnet with it, different reed switches are closed and by determining which switches are open or closed the position of the spring and thus the flow rate can be approximated.

[0082] 6.4. Inductive Sensors A conductive plate is positioned on the moving end of the spring, and an inductive coil generates a closely spaced electromagnetic field. As the distance between the coil and the plate changes, the inductance of the system changes, which can be analyzed by software. This can be used to approximate the position of the spring and, therefore, the flow rate.

[0083] 7. Pinwheel anemometer 7.1. A pinwheel is positioned within the chamber and its rotational speed varies with changes in flow rate. The rotational speed of the pinwheel can be monitored by a rotary contact switch, the periodic disruption of a light curtain, or a combination of a magnet and a Hall effect sensor, and can be used to approximately determine the flow rate through the chamber.

[0084] 8.Heating surface 8.1. Hot wire anemometer A wire or mesh is heated by applying a constant voltage across it. As air moves across the wire, it cools and its resistance decreases. As the voltage remains constant, the current through the wire increases, which can be monitored by electronics. The magnitude of the current flowing through the wire is then used to estimate the flow rate.

[0085] 8.2. Thin-film flow sensor It has the same principle as a hot wire anemometer, except that it is less invasive: a thin film heated sensor is placed on a surface inside the chamber, and the magnitude of the current flowing through the sensor can be used to determine the flow rate.

[0086] 9. Piezoflex Sensor 9.1. Deflection type When an airflow contacts an object, the object exerts a force on the air, causing it to change direction around the object. At the same time, the air exerts an equal but opposite force. Using this principle, a Piezoflex sensor can be used to deflect a surface as air strikes it, with the magnitude of the deflection being proportional to the amount of airflow hitting the sensor. The piezoelectric material generates a voltage when strained, and therefore the strain can be detected and analyzed using various algorithms. Higher strain indicates higher flow rates.

[0087] 9.2. Vibration type Air flowing around a blunt object may generate vortices at a specific frequency when boundary layer separation occurs. This vortex excitation can induce vibrations within the object itself; if the object is made of a piezoelectric material, a voltage can be generated at a frequency that matches the frequency of the vibrating object. This signal is analyzed to estimate the flow rate using various algorithms. Alternatively, to amplify the signal, various objects that generate vortex excitation at different frequencies with the same flow rate can be used. If the excitation frequency matches the resonant frequency of the object, large amplitude vibrations will be induced, which may be easy to detect and analyze.

[0088] 10. Multi-stage contact switch 10.1. Different switches can be closed in different steps. Multiple printed conductive paths can be printed on a flexible surface, and different switches can be closed at different positions on the flexible member. Depending on which paths are closed or open, the position of the flexible member can be estimated, and therefore the flow rate.

[0089] 11. Potentiometer vane 11.1. The vane can be designed to use the flow-induced force described in embodiment 9.1 to adjust a potentiometer (variable resistor or voltage divider) when flow is present. A biasing spring makes the vane position dependent on the flow present. The resistance of the potentiometer can be continuously monitored, and the flow rate can be estimated based on this measurement.

[0090] MDI operation detection Detection of MDI actuation is important information that can be used for dose assurance and to provide feedback to the user regarding optimizing the user's breathing technique. Several characteristics of the MDI can be used to detect MDI actuation, including the visual appearance of the aerosol plume, its sound, the temperature drop associated with rapid HEA propellant evaporation, its force to fire, the dielectric constant of the aerosol, its displacement to fire, its pressure at actuation, or communication with smart features located on the MDI itself, as described in various embodiments below.

[0091] 1. How to use light 1.1. Light Transmission (AKA Light Curtain) Referring to Figures 7 and 8, in one embodiment, the light source (e.g., a blue LED) 39 and photodetector (photodetector) 32 are oriented with a distance from each other so that the source is directed toward the detector with an air gap between the source and detector, or so that light from the source can be detected by an activated detector. Any wavelength within the visible and / or infrared spectrum can be used to detect MDI activation. This air gap is large enough that, when the MDI is activated, the aerosol plume is minimally obstructed by the presence of the source and detector. As the aerosol plume moves between the source and detector, the amount of light from the source reaching the detector decreases as the aerosol scatters and reflects the light away. This results in a sudden change in the detector output, the signal of which can be analyzed by various software algorithms. In particular, the aerosol drug particles scatter, reflect, and / or absorb blue light to varying degrees within the interior space of the chamber. The change in light is detected by the photodetector, which transmits a signal to a processor. When no aerosols are present within the interior space, the photodetector records a baseline reading of the light received. If there is activation due to light scattering / reflection / absorption, the photodetector receives less or more light. Depending on these parameters, the smart VHC can accurately determine MDI activation. This event can further be used to record a timestamp, which may be useful for tracking and monitoring compliance. As shown in Figure 8, the photodetector's output over time provides a reliable indication of activation as evidenced by periodic spikes on the timeline.

[0092] The wavelength of the light source can be any wavelength, ideally from the infrared bandwidth, so that the light is not visible to the user and does not distract the user. The sensitivity of the photodetector should be such that it is most sensitive to light emitted by the light source. An ideal light source would have a wavelength within the infrared spectrum (wavelengths between 700 nm and 1 mm) or the visible spectrum (wavelengths between 400 nm and 700 nm) and take the form of an efficient light-emitting diode (LED).

[0093] An ideal photodetector would have the highest sensitivity to the wavelength of the source light, and such an ideal photodetector may include a photodiode, phototransistor, or photosensitive resistor (LSR).

[0094] 1.2.Light reflection The light source and photodetector are oriented so that the detector only receives light from the source when a reflector or medium is present. When an aerosol plume is present, light from the source is reflected, and at least a portion of this reflected light is absorbed by the detector. This spike in light absorption at the detector results in a voltage change that can be analyzed by various software algorithms. The light source and detector should have the same characteristics as described for the light transmission embodiment.

[0095] 1.3. Color reflection The white light source and color sensor are oriented so that the color sensor accepts light only after it strikes an object or medium and is reflected. When an aerosol plume is present, it reflects some wavelengths of light while absorbing others. All combinations of reflected wavelengths indicate the color of the aerosol plume, which can be detected by the color sensor. The sensor can detect sudden changes in light levels as well as color, which can be analyzed with various software algorithms to detect MDI activation.

[0096] 1.4. Camera and Image Processing Cameras and image processing tools are used in a wide range of applications, of which aerosol plume identification is one application. A variety of software algorithms can be used.

[0097] 2. Sound-based method 24-28, the VHC or its associated backpiece 8 includes a microphone 82 (activation detector), an acoustic interface, a visual feedback indicator 40, a microcontroller (which may be a processor 502), a memory device 504, a limit switch, Bluetooth / Wi-Fi connectivity, and a battery 503, all of which may be housed within the backpiece 8. The limit switch 62 detects the presence of an MDI, which triggers the electronic system to power up. The microphone and acoustic interface record sounds within the internal cavity. When the MDI is activated, all sound waves of the activation are captured by the microphone 82 and stored in memory for analysis.

[0098] For all sound embodiments, a second microphone may be used to pick up ambient noise, and the signal from this microphone may then be used for noise reduction purposes for the signal under analysis.

[0099] 2.1. Microphone - Simple Volume Threshold A microphone is placed near the mouthpiece of the MDI, and the microphone is at least partially insulated from external environmental sounds. During MDI actuation, a relatively loud sound is generated as medication is forced out of the MDI orifice, and this spike in volume can be detected using various software algorithms.

[0100] 2.2. Microphone - Pre-filtering Volume Threshold Simple volume threshold methods are subject to false triggering as a result of any loud sounds from the environment that are not adequately attenuated by sound insulation. To further reduce the risk of false triggering, the volume threshold can be combined with a pre-filtering process of the incoming microphone signal.

[0101] The sound produced during MDI operation is composed of a variety of sound frequencies. Low-pass, high-pass, or band-pass filters are used to condition the microphone signal so that only frequencies associated with MDI operation are heard. This limits the possibility of false triggering for loud sounds that fall within the sound bandwidth of MDI operation.

[0102] A microphone is placed near the mouthpiece of the MDI, and the microphone is at least partially insulated from external environmental sounds. The microphone's output signal passes through a series of carefully selected resistors, capacitors, and / or inductors arranged in such a way as to form low- and / or high-pass filters. After passing through these filters, the signal is analyzed by a microcontroller (FIG. 28) or other processor 502 for spikes in volume that can be detected using various algorithms. The frequency filtering process can also be accomplished digitally.

[0103] 2.3. Microphone-to-Target Signal Comparison (Filtered and Unfiltered) Both methods (2.1. and 2.2.) are triggered as a result of loud ambient sounds. Quantitative comparison of the incoming sound with a predefined target, instead of or in conjunction with a simple volume threshold, can nearly eliminate the risk of false signals. Autocorrelation and least mean squares are the few time-domain based algorithms that can be used for signal comparison, and both of these can be combined with analog or digital filters, as described in embodiment 2.2., or with no filtering at all. Frequency-domain algorithms can also be used to compare sources and targets.

[0104] 3.Temperature change method 3.1. Temperature Sensor and Direct Contact Evaporation MDIs typically contain propellants with low boiling points, such as hydrofluoroalkanes (HFAs). During MDI operation, some of this propellant can escape the MDI in its liquid phase. When this liquid propellant is exposed to the external environment, it evaporates rapidly as a result of its low boiling point and the propellant's minimal vapor pressure in the ambient atmosphere. Evaporative cooling causes a rapid drop in temperature in all materials in contact with the liquid propellant.

[0105] Referring to Figures 38 and 39, one embodiment of a VHC and / or MDI includes one or more temperature sensors 140 (operation detectors), such as those coupled to, embedded in, or located within the wall of the holding chamber, e.g., on the inhalation valve or baffle at the output end of the chamber housing. The temperature sensor may be a temperature-sensitive resistor, thermocouple, thermistor, or infrared temperature sensor to detect a sudden drop in temperature and subsequent warming. Alternatively, a sudden drop in temperature alone may be sufficient. This rapid temperature drop and / or rewarming can be detected using various software algorithms. In this embodiment, the temperature sensor is positioned in the path of the aerosol plume so that a certain amount of liquid propellant is deposited on its surface. Care is taken to avoid substantial drug loss from the sensor within the aerosol path. A sensor with minimal thermal mass is ideal to facilitate rapid detection of temperature changes. As shown in Figure 39, different minimum plume temperatures may be associated with different MDI formulations. The temperature data may then be input to a microcontroller or other processor 502 (not shown) to direct MDI operation and for recording.

[0106] 3.2.Temperature Sensor and Air Temperature In embodiment 3.1, a temperature sensor must be located in the aerosol path during MDI actuation. Alternatively, a rapid drop in air temperature may be monitored, since evaporation of propellant also reduces the ambient air temperature. For example, as shown in FIG. 38, a sensor 140 may be placed outside the interior space of the holding chamber on the MDI. This allows for a non-invasive method of MDI actuation using temperature. The location of the temperature sensor must be close to the MDI, since the magnitude of the temperature drop decreases with increasing distance from the MDI. This is the result of the evaporation of most of the propellant prior to long-distance travel. The ratio of temperatures at different distances from the MDI or a temperature-distance profile may be evaluated using multiple temperature sensors positioned along the chamber to obtain greater reliability in detecting MDI actuation.

[0107] 3.3.Temperature sensor installed in MDI As shown in Figure 38, immediately after actuation, the propellant is not in phase equilibrium. This causes some of the liquid propellant to evaporate, eventually saturating and restoring equilibrium. Evaporation causes the canister temperature to drop, which can be detected using the contact temperature sensor mentioned in embodiment 3.1 or any other sensor. This may be built into the MDI adapter or may be an over-the-counter add-on to an MDI canister with wireless communication capabilities for communicating with the MDI adapter. The temperature data can then be input to a microprocessor or other processor 502 (not shown) to direct and record MDI actuation.

[0108] 4. Launch force 4.1. Local force peak detection Referring to Figures 40-42, a force sensing resistor (FSR) or actuation detector located at the top or base of the MDI boot may be used to obtain force measurements to detect MDI actuation. Referring to the force versus displacement curve for the canister in the boot, as shown in Figure 42, there may be a peak or other signal change at the time of actuation that can be detected using the FSR and various algorithms. Several types of force sensors may be used in addition to the FSR, including strain gauges, spring-displacement sensors, piezoflex sensors, and others. As shown in Figure 40, a force sensor 160 is located on the support flange of the backpiece 8. In Figure 41, the force sensor 160 is coupled to the backpiece with a tether 162 and located on a cap 164 secured to the top of the container 28, where the force sensor engages the user during MDI actuation. The force sensor 160 communicates signals to the computer 500 and processor 502.

[0109] 4.2. Force Threshold A simple force threshold can also be used in place of the peak finder, although this method may be less reliable.

[0110] 5. Capacitance change 5.1. One factor that affects the capacitance of the capacitor 106 is the dielectric constant of the material between the two charged surfaces. Assuming that the dielectric constant of the medical aerosol is different from that of air, changes in the capacitance of the integrated capacitor can be used to detect MDI actuation. Referring to Figures 43 and 44, the capacitor has an open gap that allows aerosol from the MDI to easily penetrate. The capacitor can be placed at the output end, as shown in Figure 43, or at the input end, as shown in Figure 44. The capacitance is then monitored for changes using an oscillation or charge / discharge circuit where a sudden change in frequency signals MDI actuation. This can be detected using various software algorithms. The capacitor is in communication with the computer 500 and processor 502.

[0111] 6. Displacement for firing 6.1. Magnetic Caps and Reed Switches Referring to Figures 45A and 45B, a canister cap 170 fits securely onto the MDI canister in approximately the same position as the dose counter and moves with the canister during actuation. The cap has magnetic properties, either by being printed with magnetic ink or by having a permanent magnet embedded within its structure made of magnetic material. A Hall Effect sensor or reed switch 172 is provided within the MDI adapter. When the MDI canister is pressed into its actuation position, the reed switch closes, which is detected by software. The Hall Effect sensor can be used to analyze the signal for the presence of a plateau, signifying the MDI canister bottoming out or a change in X or actuation point. The sensor is in communication with the computer 500 and processor 502.

[0112] 6.2.Conductive Caps and Inductors As in embodiment 6.1, a cap is sold with the VHC. In this embodiment, the cap is conductive; it is not necessarily magnetic. The oscillating electromagnetic field is created by an inductor located within the chamber inducing a current in the MDI canister cap. As the cap moves closer to the inductor during actuation, the inductance of the system changes, which can be detected and analyzed. Once a plateau in the signal is reached, signifying canister bottoming, the actuation can be recorded by software.

[0113] 7. Pressure detection When an MDI is actuated, its pressurized contents are forced out the nozzle and into the VHC. The accompanying pressure waves can be detected by a pressure transducer 78 located within the chamber or near the mouthpiece of the MDI itself, as shown in Figure 18. In particular, one or more pressure sensors 78 are located on or along the interior surface of the wall within the interior space of the chamber. Referring to Figure 20, the relationship between pressure sensor output and time indicates when actuation has occurred as evidenced by a spike.

[0114] 46 and 47, a pressure sensor 78 may be provided within the interior space at either the input or output end of the holding chamber. The sensor detects and records pressure differences.

[0115] 48, one or more flow channels 84 are positioned adjacent to a support block 86 with their discharge orifices 88. Ambient air enters entrained through the flow channels, providing a flow path of known resistance. A pressure sensor 78 records the pressure difference.

[0116] 49 and 50, a restrictor orifice is created in the bypass channel. The pressure drop across the restrictor orifice can be detected and recorded by a pressure sensor, which can then be correlated to flow rate. The various pressure sensors are in communication with a computer 500 and a processor 502.

[0117] 8. Communication with Smart MDI 8.1. Referring to Figure 78, the MDI may include a dose counter module 90 that is activated for compliance monitoring purposes and captures dose activation time, counts, and total amount. At the same time, the VHC may include a flow detection module 92 that captures inspiration time, duration, and counts, the module being in communication with, for example, Bluetooth technology. Communication with these devices from the smart VHC or its use can be used to detect and verify MDI activation and technology.

[0118] Referring to FIG. 13, activation of the MDI is detected by receiving a signal from a transmitter 221 located on top of the MDI canister. Upon activation, the transmitter outputs a signal that is received by the smart VHC. For example, a piezoelectric disk attached to the top of the canister, either integrated into a dose counter coupled to the container or provided as a separate element, generates a voltage sufficient to power the transmitter when pressed. Several types of transmitter / receivers are possible, including an IR LED / photodiode, a radio frequency (RF) Tx / Rx, or an audio transmitter / microphone. Depending on the type of Tx / Rx, this system can also be used to identify the MDI type, with different RF frequencies used for the controller / rescuer inhaler.

[0119] MDI Insertion Providing feedback and confirmation to the user that the MDI has been properly inserted can be a desirable feature of a smart VHC. Additionally, depending on the method used, this feature can determine when the microcontroller or other processor 502 is asleep, further extending the device's battery life. As an example, when an MDI is inserted, the microcontroller wakes up and draws current from the power source to power its sensors, display, and communication devices. Once removed, the microcontroller returns to a low-energy state.

[0120] 1. Switch 1.1.Limit / Contact Switches In this embodiment, as shown in FIG. 19, a limit switch 62 (mechanical) or contact switch is positioned within the backpiece 8 in a manner that closes the switch upon insertion of the MDI. The limit switch closes a circuit when the MDI is inserted. This switch closure triggers an interruption of the microcontroller or other processor 502, allowing the microcontroller or other processor to operate in its fully operational state, at which point the user is notified by a visual or auditory cue that the MDI is fully inserted. When the MDI is removed, the switch opens, causing the microcontroller to return to its low energy requirement state. In one embodiment, if the device is inactive for a predetermined period of time, e.g., approximately 30-120 seconds, the microcontroller can enter a sleep mode. The predetermined period can be set / programmed by the user.

[0121] In addition to contact switches, see Figure 11, buttons can be used to power the system on and off. Audio or visual feedback mechanisms, such as visual or audio indicators, e.g., lights and / or alarms, can be implemented using various LEDs, speakers, and tactile and / or visual displays / indicators.

[0122] 1.2.Reed Switch As in embodiment 1.1, referring to Figure 74, a portion 200 of the MDI is magnetized, either with magnetic ink, an electromagnet, or a permanent magnet. When the MDI is inserted, a reed switch 202 is closed. Opening and closing this switch has the same consequences for microcontroller operation and user feedback as described in embodiment 1.1.

[0123] 1.3.Conductive Path In this embodiment, as shown in Figure 75, a portion of the MDI, e.g., the mouthpiece, has a conductive path 204 that, when inserted into the MDI adapter, closes a circuit 206 in the MDI adapter electronics. This circuit is used to provide feedback to the user and to enable full functionality of the controller as described in embodiment 1.1.

[0124] 2. Light curtain 2.1. A light curtain, as described above, can be used to determine the insertion of an MDI into an MDI adapter. In this embodiment, an LED and a photodiode are positioned on opposite sides of the MDI adapter opening. When an MDI is not inserted, light from the LED can reach the photodiode. Once an MDI is inserted, this light transmission is blocked, which can be detected by a microcontroller and used to provide audible or visual feedback to the user to ensure proper insertion of the MDI.

[0125] 3. Mouthpiece shape detection 3.1.Strain gauge Strain is introduced into the MDI adapter or backpiece as shown in Figure 70 when the material deforms to accommodate the MDI mouthpiece shape. The magnitude of the strain can be measured using a strain gauge 206. Monitoring the strain on the MDI adapter can provide one way to determine if an MDI has been inserted into the MDI adapter. Once the strain reaches a certain threshold, the system provides feedback to the user to confirm MDI insertion.

[0126] 3.2. Force sense resistor (FSR) The force sense resistor 208 may be located on or in the MDI adapter or backpiece 8 as shown in Figure 72. Upon MDI insertion, the MDI mouthpiece exerts a force on the FSR, which causes a voltage change that is evaluated by the microcontroller. Depending on the signal coming from the FSR, insertion of the MDI can be concluded and this information is relayed back to the user.

[0127] 3.3. Linear Action Potentiometer A linear action potentiometer 210 may be positioned on or within the MDI adapter or backpiece as shown in Figures 69 and 71. Upon MDI insertion, the potentiometer displaces, causing a voltage change that is evaluated by a microcontroller. Depending on the signal coming from the potentiometer, it concludes the insertion of the MDI and relays this information back to the user.

[0128] 4. Image Processing 4.1 A camera or series of cameras can be used to determine how far the MDI has been inserted into the MDI adapter. Various image processing algorithms can be used to determine this and once verified, this information can be relayed back to the user.

[0129] Power Supply and Distribution Problem Identification

[0130] All embodiments require the use of electrical power to function. Various power sources can be used on their own or in combination with other sources. Sensors and feedback methods can receive power even if they are located on separate chamber components.

[0131] power supply source 1. Battery (single or multiple batteries can be used for each) 1.1. Permanent, disposable The power supply may be such that once the battery is depleted, the entire electronic device is disposed of. The battery is permanently enclosed within the electronics body with limited access so that access does not damage the electronic device.

[0132] 1.2. Exchangeable The power supply may be such that once the batteries are depleted, the user can access the battery cartridge and replace the depleted batteries with charged batteries, similar to many children's toy or watch batteries.

[0133] 1.3. Rechargeable The battery may be rechargeable so that once the battery is depleted, the user can simply charge it via a DC power jack, USB, or other method. Additionally, the battery may be trickle charged throughout its lifespan, thereby extending its time to depletion. Trickle charging refers to periodically charging the battery continuously or with a very weak current. This type of charging alone takes a very long time to fully charge a depleted battery, but is useful for extending battery life, especially if charging occurs continuously.

[0134] 2. Photovoltaic cells 2.1 Photovoltaic cells generate a voltage in response to light, which can be used to power a device directly or to charge a battery or supercapacitor depending on the power requirements of the sensors and features.

[0135] 3. Rectenna 3.1. Rectennas induce weak electrical currents in the antenna that are rectified and managed so that they can trickle charge a rechargeable power source using ambient radio frequency energy such as wireless transmissions, mobile communications, and Wi-Fi networks.

[0136] 4. Shake to charge 4.1. By incorporating a freely moving magnet within a conductive coil, the system can induce a current in the conductive coil when the device is shaken or the magnet is moved by other means. The motion of the magnet induces a current in the coil, which can be used to charge a battery or other power source.

[0137] power distribution It is preferable to have all the electronic components close together to make power distribution easier to manage. However, given the requirements of the device, this may not be possible. There are some power distribution schemes where some electronics are housed in the MDI adapter while others are housed in the mouthpiece or mask adapter.

[0138] 1. Conductive paths along the object 1.1. This method uses only one power source (e.g., a single battery) located in either the mouthpiece / mask adapter or the MDI adapter, with power transmitted through the object to the other components. In either case, contacts with both ends of the object ensure that power is transmitted to the other components. The contacts are formed in a manner that allows for a repeatable and robust connection with each assembly while still allowing for assembly and disassembly of the device for cleaning. These conductive paths are also used to allow data communication between the hardware located in front and the microcontroller located behind.

[0139] 1.1.1.Conductive resin Conductive resins can be used to mold conductive pathways directly into object components, using dual-shot or insert molding manufacturing methods.

[0140] 1.1.2.Conductive ink Conductive inks can be used to form conductive paths and can be pad or screen printed onto objects.

[0141] 1.1.3. Flexible Electronics and Adhesives Flexible, low profile electrical wires can be used and these can be secured to the object with the use of adhesive.

[0142] 2. Two batteries with wireless communication 2.1. The hardware at the mouthpiece / mask adapter end of the VHC may be powered by a completely separate power source (e.g., a battery) from the power source at the MDI adapter end of the VHC. Each end of the chamber would likely need its own microcontroller or other processor 502 to handle the inputs and outputs at their respective ends. In this manner, the two microcontrollers will most likely need to communicate with each other to share data. This may be done via Bluetooth or other means.

[0143] MDI identification Identification of MDIs provides patients, prescribers, and payers with assurance of compliance with approved medical regimens. Additionally, it can be used to alert patients if the wrong medication is inserted into the chamber, thereby helping to prevent under- or over-dosing of certain medications. The identification methods described below can be used by themselves, but can also be used in combination to reliably identify MDIs.

[0144] For example, referring to FIG. 13 , a photodiode 222 and a color detector sensor 224, or MDI identification device, may be located on the exterior surface of the chamber housing wall or backpiece and may be directed toward the MDI, including the actuator boot and container. A unique tag 226 may be attached to each MDI, or a unique rescue tag may be attached to the rescue MDI and a unique controller tag may be attached to the controller MDI. The sensor 224, e.g., a color detector sensor, detects the presence of the tag to identify each specific MDI or to identify each MDI by category, e.g., rescue or controller. The tags may have distinct colors, bar codes, magnetic properties, surface properties, e.g., reflection / absorption, etc.

[0145] 1. MDI boot color detection 1.1.Mouthpiece color Referring to Figure 68, MDIs are sold in a wide variety of colors, some with two hues that distinguish the handle from the mouthpiece. Color sensing involves detecting a specific color code reading (e.g., RGB, CMYK, L) from the mouthpiece portion of the MDI. * a * b * ) can be used to help identify an MDI inserted into an MDI adapter. When an MDI is inserted into the adapter, color-sensing hardware or sensor 224 (MDI identifier) ​​is triggered to collect color information from the mouthpiece of the MDI. This color code is then analyzed by software and compared to a database of MDIs and their respective color codes. Various algorithms can be used for the comparison, and the closest match is used for MDI identification. Alternatively, the MDI boot color code can be used as an input to a multi-factor algorithm, which uses several inputs to identify the MDI.

[0146] 1.2.Handle color As shown in FIG. 68, similar to mouthpiece color detection, but instead of positioning the color sensor 224 to obtain the mouthpiece color code, the color sensor is positioned to analyze the color of the handle portion of the MDI boot.

[0147] 1.3.Mouthpiece and handle color The combination of embodiments 1.1 and 1.2 helps distinguish two-tone MDI boots.

[0148] 2.Color detection of aerosol plumes 2.1. There are countless pharmaceutical formulations across all MDIs, which may be reflected in different color codes of the aerosol plume. Color sensing hardware is positioned near the mouthpiece of the MDI boot in the MDI adapter to collect the color codes of the aerosol plume during MDI operation and compare these to a database of different MDIs. Various comparison algorithms can be used, and the closest match is used for MDI identification. Alternatively, the aerosol color code can be used as an input to a multi-factorial algorithm, which uses several inputs to identify the MDI.

[0149] 3. Mouthpiece shape detection 3.1. Force sense resistor (FSR) Referring to Figure 72, the FSR 208 is positioned within the MDI adapter so that during MDI insertion, the resistors are compressed an amount proportional to the size of the MDI mouthpiece in that particular orientation, causing these signals to change accordingly. These resistance values ​​are compared to the resistance values ​​of MDIs in a database. Various comparison algorithms can be used, and the closest match is used for MDI identification. Alternatively, the resistance values ​​can be used as input to a multi-factor algorithm, which uses several inputs to identify the MDI.

[0150] 3.2.Strain gauge The MDI adapter port is intentionally undersized so that it must stretch when an MDI is inserted, as shown in Figure 70. The total strain, both large and small, detected by the strain gauges 208 and their locations can be analyzed and compared to a database of different MDIs and their strain values ​​to aid in identifying the MDI.

[0151] 3.3. Referring to Figures 69 and 71 and the linear action potentiometer 210 similar to the FSR method, the linear action adjusted potentiometer is adjusted according to the size of the MDI mouthpiece in a particular direction. The resistance value collected by the system upon MDI insertion is compared to values ​​stored in a database for various MDIs. These potentiometers have biasing springs that return them to their original position when the MDI is removed.

[0152] 4. Mouthpiece length 4.1. Tactile or Slide Potentiometer The length of the mouthpiece portion of the MDI can be used as a distinguishing factor.

[0153] Upon full insertion into the MDI adapter, the length of the mouthpiece can be measured by feel or by a sliding potentiometer and compared to various lengths stored in the system's database shown in FIG.

[0154] 5. Resistance to flow profile 5.1. Resistance to Flow Profile 54 and 55, the flow rate through the chamber can be monitored by various sensors as disclosed herein. The flow rate can be used to help identify the MDI. Using this flow rate information combined with data from the differential pressure sensor 78 to compare the pressure at the MDI mouthpiece to atmospheric pressure, a pressure vs. flow rate profile can be compiled for the MDI. This profile can be compared to profiles in a database of MDIs to find a match that can identify the MDI. Alternatively, the resistance profile can be used as an input to a multi-factorial algorithm.

[0155] 6. MDI sound at a certain flow rate Referring to Figures 24-28, the audio interface includes an equalizer circuit (e.g., 7-band) that divides the audio spectrum into seven bands, including, but not limited to, 63 Hz, 160 Hz, 400 Hz, 1 kHz, 2.5 kHz, 6.25 kHz, and 16 Hz. The seven frequencies are peak-detected and multiplexed to the output, resulting in an indication of the amplitude of each band. The bands are processed by a microcontroller to average the bands into a single amplitude (dB) and time signal (Figure 25). The unique sounds produced by different brands of MDIs can then be compared to known sounds stored in a memory device or cloud database. Normalized correlation techniques can be used to accurately compare the input sound to a reference sound. Operational sounds can be captured and stored during MDI operation, and comparisons and assessments can be processed post-treatment, freeing up processing power for other VHC tasks during treatment, depending on available processing resources. If the process is fast enough, the MDI actuation will be analyzed in real time and provide feedback as to whether the MDI nozzle or support block is plugged or partially plugged due to low or insufficient sound produced. The feedback may also include information as to whether the MDI needs to be shaken and / or primed or checked for an adequate remaining dose count.

[0156] 6.1. A database can be created containing the frequency spectrum or dominant frequencies of all MDIs at a particular flow rate. In use, when this flow rate is reached, the sound is sampled by a microphone and compared to the sound profile stored in the system database. Various algorithms can be used for this comparison.

[0157] 7. MDI sound when operating 7.1. A database can be created containing the frequency spectrum or dominant frequencies of all MDI actuation sounds. When an actuation occurs, the recorded sound is quantitatively compared with the sounds stored in the system's database to find the closest match.

[0158] 8. MDI sound during a collision 8.1. A database can be created containing the frequency spectrum or dominant frequencies of all MDI sounds upon impact or strike. Upon insertion into the MDI adapter, a mechanical hammer is triggered, which impacts the MDI within the mouthpiece area. The sound produced depends on the shape, volume, and stiffness of the MDI boot and its fit with the MDI adapter. This sound can then be quantitatively compared with the sounds in the system's database.

[0159] 9. Image Processing 9.1. Label Reading Text recognition software is used to "read" the text on the MDI boot and / or MDI canister. For example, referring to FIG. 4, a camera 35 or other image sensor (MDI identifier) ​​is mounted on the chamber housing, e.g., adjacent to or anywhere between its input or output end. The image sensor may also be coupled to the mouthpiece assembly or backpiece. The camera or image sensor captures an image of the MDI, including various textual information provided on a label 240 coupled to the container and / or activation boot. Image processing algorithms and / or machine learning techniques can be used to extract unique shapes and / or unique features indicative of the textual information, type, and identity of the MDI associated with the VHC. The captured image may then be stored in memory and compared to various types of MDIs in a database to narrow the selection. Referring to FIGS. 5A, 5B, and 6, the camera or image sensor captures an image of the MDI and converts it into a grayscale image 242, as shown in FIG. 5B. The processor then extracts multiple (e.g., three) templates from the captured grayscale image and compares the templates / images with stored images in a database. As shown in Figure 6, the processor accurately identifies the MDI by referencing the label 244.

[0160] 9.2. Combining Colors and Shapes The color and shape from a digital image or series of digital images are analyzed and compared to the colors and shapes of various MDIs in a database.

[0161] 9.3.Feature Recognition An image kernel can be used to scan an image for similarities to the kernel itself. For example, using a kernel in the form of a GSK label, a GSK boot can be identified by computing a correlation result for each position of the kernel on the image and determining whether the correlation coefficient exceeds a certain threshold, which indicates a good match.

[0162] 10. Spectroscopic Drug ID 10.1. Single wavelength infrared / UV Infrared and ultraviolet spectroscopy are methods used to determine the chemical structure and composition of a sample. All chemicals absorb infrared and ultraviolet radiation to some extent, and absorb some wavelengths of light more than others depending on the bonds present in their chemical structure. Using a light source of controlled wavelength, the drug's absorption rate for specific wavelengths can be analyzed by shining light through the aerosol toward a photodetector. This absorption rate can then be compared to values ​​in the MDI database.

[0163] 10.2.Multi-wavelength infrared / UV Same as 10.1., except multiple wavelengths can be used.

[0164] 11. Launching power 11.1. A force sensing resistor (FSR) can be used to determine the force during MDI actuation. This needs to be coupled with MDI actuation detection as described herein. Upon detecting MDI actuation, the force is recorded and compared to the value stored in the MDI database.

[0165] 12. Aerosol temperature (aerosol / air temperature or contact evaporation) 12.1. Single Location Temperature can be monitored at a fixed distance from the MDI, and the temperature detected during MDI operation can be used to compare this information with temperatures stored in the system's MDI database. Despite all MDIs using the same propellant family (HEA134a or HFA227), aerosol temperature differences will be visible at a fixed distance from the MDI as a result of the different drug formulations.

[0166] 12.2. Relationship between temperature and distance In addition to embodiment 12.1, several temperature sensors can be used at fixed distances from the MDI to collect a temperature profile during operation of the MDI. This profile can be used and compared to profiles in the system's database.

[0167] 13. RFID implemented in MDI from supplier 13.1. Referring to Figure 73, a radio frequency identification (RFID) tag or label 252 may be affixed to or molded into the MDI by the drug manufacturer or supplier, in which case the RFID label on the MDI can be read by an RFID reader 250 provided in an MDI adapter or coupled to the backpiece 8 or other part of the VHC.

[0168] 14. RFID implemented in dose counters (integrated or OEM) 14.1. Similar to embodiment 13.1., RFID tags may be integral or incorporated into the dose counter module, which may be read by an RFID reader incorporated within the chamber.

[0169] 15. Labels placed on the MDI by the user RFID

[0170] As in embodiments 13.1 and 14.1, the RFID tag may be read from the MDI. In this embodiment, the RFID is sold in the form of a sticker, adhesive patch, or other form that is placed on the MDI by the user.

[0171] 15.2. Barcodes (1D and 2D) Similar to embodiment 15.1, except that a barcode is used instead of an RFID. In this case, the chamber has a barcode scanner as opposed to an RFID reader.

[0172] 16. Access to patient medication lists in the cloud 16.1. Bluetooth / Wi-Fi Access The user's digital medical record can be accessed via the Internet, and these MDI drug prescriptions can be used to help identify MDIs to be used in conjunction with the VHC. Alternatively, to ensure security, the healthcare provider or payer may activate a "profile" for the user to select the user's MDI medications, which are then transmitted to the VHC via Bluetooth or Wi-Fi.

[0173] 17. Communication with smart inhalers 17.1. Bluetooth (registered trademark) / Wi-Fi communication Smart inhalers are already being used to track MDI adherence. Communication with these inhalers allows VHCs to directly identify the MDI being used. This can be achieved through Bluetooth or Wi-Fi communication.

[0174] 18. Manual selection by the user 18.1. Manual Selection Referring to FIG. 19, user input buttons 260 are shown, e.g., with different colors, shapes, or labels. The user 66 presses the appropriate button associated with the rescue MDI, e.g., the blue button associated with the rescue MDI, or the red button associated with the controller MDI. The combination of pressing both buttons transmits the MDI in the combination state being used. Each button may also have a visual indicator, e.g., a light, which, when pressed, illuminates and remains illuminated for a predetermined period of time (or until the treatment or procedure is completed). If an incorrect indicator is displayed, a start-over indicator is provided to the user. A single button may also be used, in which pressing the button is associated with either the rescue or controller MDI, and not pressing the button is associated with the other type of MDI. When reviewing patient usage data, the prescriber will know which medications are associated with each of the rescue and controller MDIs. Additionally, the user can enter medication information on the computer using an application, e.g., in a user profile setting. The user can share logged medical activity with the prescriber and / or payer.

[0175] The user may be given the option to manually select the MDI to be employed. This selection can be performed at the time of each administration or can be specified once by the user when the list of medications is received in the smart chamber. For users prescribed only one medication, the latter method serves to reliably identify the MDI to be used at any given time, whereas for users prescribed multiple medications, this can be used to provide a short list of possible MDI candidates that then need to be further identified by the system using the means described in other embodiments.

[0176] 19. Capacitance / Dielectric Constant Detection 19.1.Dielectric constant detection Two oppositely charged features are separated by an air gap that forms an open capacitor. When the MDI is activated, the air gap is filled with aerosol. Assuming that aerosols have different dielectric constants, the change in capacitance of the open capacitor can be measured, and this capacitance value can be matched with capacitance values ​​in a database of known aerosols and used to identify the MDI.

[0177] 20. Resonant frequency of MDI 20.1. A tone generator is placed within the VHC, which produces a range of frequencies in a sweeping manner. When the tone generator produces a resonant frequency of the MDI, a spike in volume may occur, which can be detected by a microphone.

[0178] 21. Infrared reflectivity of MDI boots 21.1. Infrared (IR) emitters and IR detectors can be used to generate infrared "signatures" for various MDIs. The IR emitters and detectors and their positioning can be identical to the white LEDs and color sensors described above and shown in the accompanying figures. IR radiation is directed toward the mouthpiece and / or handle portion of the MDI boot, and the amount of absorbed / reflected radiation is used to identify the MDI. Specifically, in this embodiment, the amount of reflected radiation is detected by an IR detector, and this value is compared to values ​​present in a pre-recorded MDI database. The material of the MDI boot, its shape, and surface finish all play a role in the amount of reflected IR radiation. A single wavelength IR LED / detector can be used, or several IR LEDs / detectors with different IR wavelengths can be used.

[0179] Mask Force and Seal Feedback A face mask 600 is often used to deliver respiratory medication to a user. For example, the face mask may be coupled to the mouthpiece assembly 12 or output end of the VHC 3. To maximize medication delivery, it is important to ensure a proper seal is formed between the mask and the user's face 602. A proper seal can be determined by measuring the force applied to the mask, VHC, or other delivery device, such as a nebulizer or OPEP device, or by recording the contact between the mask and the user's face.

[0180] In one embodiment shown in FIG. 29 , the drug delivery system includes a drug delivery device, e.g., a VHC, having an input end 10 and an output end 14. A mask 600 is coupled to the output end. The mask and delivery device are movable along a longitudinal axis 6 to a position for engagement with a user's face 602. A force sensor 604 is provided between the mask 600 and the input end 10 of the drug delivery device. For example, the force sensor 604 can be provided between the mask 600 and the valve assembly 12 (e.g., a mouthpiece assembly) or between the valve assembly 12 and the chamber housing 2. The force sensor 604 can be a load cell that converts mechanical deformation or displacement into an electrical signal using a strain gauge or piezoelectric sensor, which converts changes in force into an electrical change via the piezoelectric effect. The force sensor transmits a signal to a computer 500 and a processor 502, which can be attached to, for example, the backpiece 8. The VHC microcontroller monitors the applied force and provides feedback to the user or caregiver operating the delivery device, thereby either increasing, decreasing, or maintaining the applied force. For example, the force required to achieve the desired seal may be in the range of 1.5 to 7 pounds (0.68 to 3.18 kg). Feedback to the user includes an indicator, whether a visual indicator 40 (e.g., an LED), an audible indicator (speaker), or a vibration indicator. The force sensor 604 responds to the force being applied to the mask along the longitudinal axis by the drug delivery device. The indicator provides feedback to the user regarding the amount of force being applied to the mask, whether too little, too much, and / or unevenly around the circumference.

[0181] In another embodiment, shown in FIGS. 30 and 31 , contact sensors 608, 610 may be incorporated into the mask 600 to monitor, detect, and signal proper contact with the user's face around the periphery of the mask. For example, the mask includes a sealing portion 612 adapted to engage the user's face 602. The sealing portion 612 may include an inwardly bent, C-shaped lip terminating in a free end 615. One or more sensors 608 are coupled to the sealing portion, and the force sensor responds to force applied to the sealing edge. In other embodiments, multiple sensors are embedded within the sealing portion and distributed around the periphery of the mask or along the length of the sealing portion in a spaced-apart relationship as shown in FIGS. 30 and 31 . In an alternative embodiment, shown in FIG. 30 , the sensor 610 comprises a continuous strip extending around the sealing edge.

[0182] 30 and 31, an indicator 616 is in communication with the sensor and is adapted to provide feedback to the user regarding the amount of force being applied to the sealing edge or whether contact is being made with the user's face. For example, the indicator may include a visual indicator, an audible indicator, or a vibration indicator. In one embodiment, the visual indicator comprises a plurality of lights 616 (e.g., LEDs) distributed and spaced apart along the sealing edge or perimeter of the mask. In one embodiment, the plurality of visual indicators are respectively associated with and directly coupled to the plurality of sensors.

[0183] In operation, with reference to FIGS. 32 and 33 , a user or caregiver applies force to the mask 600, engaging the user's face 602 with the mask's sealing edge 612, detecting the force being applied to the mask or, alternatively, detecting whether contact is being made at a particular location on the sealing edge, and providing feedback to the user regarding the applied force and / or contact via an indicator 616. The user / caregiver can then adjust the force being applied to the mask. In one embodiment, the feedback is the illumination of a light 616 coupled to the contact sensors 608, 610 where contact is detected and no illumination when no contact is detected. Similarly, a portion of the indicator light illuminates where the various force sensors detect sufficient force being applied, and the light is not illuminated along portions of the mask where insufficient force is being applied. In another embodiment, if too much force is applied, the light can illuminate a different color or be turned off.

[0184] Once active, the controller (which may be embodied as one or more elements of the computer 500, such as the processor 502 (FIG. 83)) can analyze the output of the force or contact sensor to estimate the quality of the seal. By combining measurements of the force being applied with measurements of contact with the user's face, the device can provide information regarding whether a proper seal has been formed.

[0185] Active Valve With various drug delivery devices, such as VHCs, taking a slow breath (up to 30 L / min) followed by breath-holding can significantly improve drug deposition in the lungs. While various acoustic aids are available to provide feedback to the user that the inhalation volume is too large, these acoustic aids are passive and do not control the inhalation volume. Therefore, these acoustic aids can be misunderstood or confused as providing positive feedback (e.g., the feedback is not intended to suggest that the user should avoid making a whistling sound, but rather that it is better to inhale quickly and make a whistling sound).

[0186] As shown in Figures 34-37, one embodiment of valve 700 actively adjusts its resistance to opening or closing during inspiration (or expiration) to actively control the volume of inspiration or expiration. The system can also provide feedback to the user that the valve is actively controlling the flow rate, allowing the user to adjust the flow rate.

[0187] The valve can be configured in a variety of forms, including an annular donut valve as shown in Figures 35 and 36, a duckbill valve 720 as shown in Figure 87, or other valves with movable, bendable, or deformable features. The annular valve has a central opening 702 and an annular flange 704 that bends or deforms outwardly to lift the flange away from the valve seat 706, thereby allowing flow through the opening 702. The duckbill valve 720 has a pair of opposed flaps 722 that open to form an opening in response to flow therethrough. The valve may be made of liquid silicone rubber (LSR).

[0188] An actuator portion 730 is attached to and embedded within the valve. For example, the actuator portion may be made of an electroactive polymer (EAP). When stimulated by an electric field, the LSR portion stiffens and resists opening. In one embodiment, the annular flange 704 of the valve includes a plurality of EAP strips 732 (shown as four). Other configurations or differently shaped portions including more or fewer strips may also be suitable. In another embodiment, at least one of the flaps 722 of the duckbill valve 720, and in one embodiment both flaps, includes an embedded electroactive polymer actuation portion 730, e.g., a strip. It should be understood that an actuator portion or EAP feature may also be attached to the exhalation or exhalation portion 731 of the valve.

[0189] The VHC or other drug delivery device has a housing 2, 12 defining a flow channel 701. A valve 700, 720 is disposed within the flow channel. The valve can move between a first and a second configuration, e.g., between an open and a closed configuration (fully or partially), in response to flow through the flow channel. The flow can be inspiration or expiration. The valve is reconfigurable between a first state and a second state in response to a stimulus, e.g., an electrical stimulus. For example, the first and second states have first and second stiffnesses or resistances to bending and / or deformation. When the valve is in the first state, the valve has a first resistance, e.g., bending or deformation resistance, to movement between the first and second configurations. When the valve is in the second state, the valve has a second resistance to movement between the first and second configurations, the first resistance being greater than the second resistance. An actuator 708 applies the electrical stimulus.

[0190] In operation, flow is created through the flow channel of the housing, for example, by a patient's inhalation or exhalation. This flow causes the valves 700, 720 to move between a first and a second configuration in response to the flow through the flow channel. Depending on the flow rate calculated by various sensors and methods described elsewhere herein, the actuator 708 can be commanded to apply a stimulus (e.g., electricity) to the valve, as shown in FIG. 34 . The valve reconfigures from the first state to the second state in response to the stimulus. Flow through the channel is altered, e.g., narrowed or increased, when the valve reconfigures to the second state, e.g., by creating greater resistance to bending or deformation, such that the opening formed by the valve or between the valve and the valve seat is narrowed or kept small.

[0191] As shown in Figure 37, the valve may be actively managed to ensure that the flow rate through the valve, sensed and detected as described above, does not exceed a predetermined threshold, for example 30L / min.

[0192] For any of the above-described embodiments of a smart device, a controller or other processing element that communicates with or controls the sensors, gauges, or switches may be incorporated into the smart device itself, positioned within or on its exterior, or located remotely from this perspective. It should be understood that various sensors, gauges, or switches can perform multiple functions and can be used in various combinations, all in communication with the controller or other processing element. Additionally, for any of the above-described smart devices, some or all of the collected data and feedback provided to the device user by the sensors, switches, or gauges can be simultaneously transmitted to a remotely located caregiver. The remotely located caregiver or monitoring agency can intervene to provide additional advice or information during the treatment session. Alternatively, the data and feedback transmitted to the caregiver or monitoring agency in parallel with the user can be remotely stored for later evaluation by medical personnel. Simultaneous transmission to a remote source, including sensed data and any feedback, can also prevent issues related to tampering with or corruption of data stored on the smart device itself.

[0193] Batteries or other power sources for any controller circuitry, sensors, meters, and switches may be rechargeable or removable in various embodiments of the smart device described herein. To minimize battery discharge, certain of the sensors may be configured for a predetermined sampling frequency rather than a continuous measurement mode. Additionally, circuitry provided in the smart device may be activated only upon detection of a specific event and may automatically switch off after a predetermined period of time from an initial trigger or after a detected period of inactivity of the device.

[0194] Although the present invention has been described with reference to preferred embodiments, those skilled in the art will recognize that changes can be made in form and detail without departing from the spirit and scope of the invention. Accordingly, the foregoing detailed description is to be taken as illustrative rather than limiting, and it is the appended claims (including all equivalents thereof) that are intended to define the scope of the invention.

Claims

1. 1. A drug delivery system comprising: a valved holding chamber comprising a chamber housing having an input end and an output end, the chamber housing defining an interior space, the output end defining an intake passage and comprising a user interface; a valve assembly coupled to the output end and defining an exhalation flow path separate from the inhalation flow path and not including the interior space of the chamber housing, the valve assembly comprising a one-piece valve having a one-way inhalation valve portion and a one-way exhalation valve portion; the inhalation valve portion and the exhalation valve portion are directly connected, the inhalation valve portion is disposed in the inhalation flow path, and the exhalation valve portion is disposed in the exhalation flow path; the intake valve portion is movable between a closed configuration and an open configuration in response to flow from the input end, through the interior space, through the intake passage, through the intake valve portion, past the user interface, and to a user interface; the exhalation valve portion is movable between a first configuration and a second configuration in response to exhalation flow through the exhalation flow path; the intake valve portion is reconfigurable between a first state and a second state in response to an electrical stimulus; the intake valve portion has a first resistance to movement between the closed and open configurations when the intake valve portion is in the first condition; the intake valve portion has a second resistance to movement between the closed and open configurations when the intake valve portion is in the second state; the first resistance is smaller than the second resistance; the inhalation valve portion prevents all backflow in the flow passage during exhalation when the inhalation valve portion is in the closed configuration; the first and second states being first and second stiffnesses, respectively; A drug delivery system characterized by:

2. Further comprising an actuator configured to apply the electrical stimulus. The drug delivery system of claim 1 .

3. the valve comprises an electroactive polymer; The drug delivery system of claim 2 .

4. the intake valve portion comprises an annular toroidal valve having an annular flange defining a central opening, the annular flange engaging a valve seat when the intake valve portion is in a closed configuration; the intake valve portion is configured with a plurality of embedded electroactive polymer strips. The drug delivery system of claim 2 .

5. the inlet valve portion comprises a duckbill valve with opposed flaps, at least one of the flaps configured with an embedded electroactive polymer portion; The drug delivery system of claim 2 .

6. the exhalation valve portion is reconfigurable between a first state and a second state in response to a second electrical stimulus; the exhalation valve portion has a first resistance to movement between the first and second configurations when the exhalation valve portion is in the first state; the exhalation valve portion has a second resistance to movement between the first and second configurations when the exhalation valve portion is in the second state; the first resistance of the exhalation valve portion is less than the second resistance; The drug delivery system of claim 1.

7. the first and second configurations of the exhalation valve portion are a closed configuration and an open configuration, respectively. The drug delivery system of claim 6.

8. the first and second states of the exhalation valve portion are first and second stiffnesses of the exhalation valve portion, respectively; The drug delivery system of claim 6.

9. Further comprising a second actuator configured to apply the second electrical stimulus. The drug delivery system of claim 6.

10. the user interface is a mouthpiece; The drug delivery system of claim 1 .

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