Systems and methods for aerosol delivery in a compact mobile format

Abstract

The present disclosure provides aerosol delivery systems, including in a compact mobile format. The embodiments disclosed herein are also generally directed towards software and methods for aerosol delivery, including dynamically tunable aerosol delivery, and including accurate real-time control variable monitoring-enabled broad-spectrum delivery, for example, of therapeutic formulations of drugs, drug mixtures, emulsions, and their combinations, over tunable, and variable concentration ranges.

Description

Attorney Docket No.81073-8002.WO00 SYSTEMS AND METHODS FOR AEROSOL DELIVERY IN A COMPACT MOBILE FORMAT BACKGROUND

[0001] The embodiments disclosed herein are generally directed towards aerosol delivery systems, including in a compact mobile format. The embodiments disclosed herein are also generally directed towards software and methods for aerosol delivery, including dynamically tunable aerosol delivery, and including accurate real-time control variable monitoring-enabled broad-spectrum delivery.

[0002] The ability to deliver a wide range of drugs, drug mixtures, emulsions, and their combinations, over tunable, and variable concentration ranges within a compact and mobile form factor in a non- destructive (non-thermal) manner currently is a limitation in capability for existing drug delivery devices. Nebulizers that utilize a vibrating mesh, ultrasonic transducer, or jet to non-destructively produce a drug solution aerosol with particle size distributions optimized for efficient pulmonary absorption are currently limited in their ability to do so over varying drug compositions, viscosity ranges, with varying environmental conditions. Furthermore, varying patient populations with variable dosing requirements and inhalation behaviors further complicate devices capacity of delivering an optimized aerosol bolus and consequentially limit the relevance of Nebulizing technology over all but a small subset of available drugs and indications.

[0003] Specific control systems and software frameworks within a compact mobile form factor are needed to generate a wide range of aerosols with targeted particle size distributions tailored to a patient’s behaviors and therapy requirements. However, in order to deploy such control systems within a mobile device, specific aerosol intermixing geometries and manifold volumes must be available / accessible by the control system in order to enable a pulmonary delivery of a wider range of therapeutic drugs and their admixtures. Specifically, there are a wide range of drug aerosols that require a minimum bolus per breath volume and require not just a specific aerosol size distribution but also a specific aerosol droplet concentration in an air diluent excipient fluid. Generating these specific volumes, droplet concentrations, and size distributions for optimized pulmonary delivery requires a minimum intermixing volume and enabling flow path geometries. Currently, no such manifold designs achieving satisfactory intermixing volume capacity and geometry for bolus aerosol-air intermixing have been developed or deployed that are capable of being integrated into a mobile form factor. Integration of this manifold design into a mobile form factor is a major limitation in the current art due to the great size of existing devices required to achieve the same results. Current device designs limit providers from realistically deploying such devices outside the hospital, or home setting.Attorney Docket No.81073-8002.WO00

[0004] In addition to the physical volume and geometric requirements of nebulizer manifold intermixing, real time monitoring of environmental conditions, patient inhalation behaviors, aerosol particle size distribution and concentrations within the manifold intermixing chamber must be accurately monitored in real time for the purpose of dynamic nebulizer actuation control. Accurate monitoring of these “control variables” in real time forms the basis of a smart control systems inputs that in combination with pre- encoded models, allow for dynamic tuning via the control system of the particle size distribution, aerosol actuation rate, particle concentration, drug concentration within each particle, and bolus size over a broad range of patient populations and conditions. Accurate real time monitoring of control variables requires measurement of real time dynamic events and aerosol properties via specific hardware sensing elements that can be translated into control variables to adjust and tune aerosol characteristics toward a target set of optimum values in a closed loop. What is critical to enabling this function is the real time measurement of aerosol properties, and how aerosol properties are adjusted dynamically via an encoded model control system framework when the medicament actuator / nebulizing element actuation waveform is adjusted.

[0005] There is therefore a need for a dynamically tunable and real-time controllable / monitorable system within a compact mobile form factor for aerosol delivery. BRIEF DESCRIPTION OF THE FIGURES

[0006] FIG. 1 is a schematic view of a computer-implemented system, in accordance with various embodiments of the present disclosure.

[0007] FIG. 2 is a schematic view of a computer implemented system, and an associated software module of the computer-implemented system, for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0008] FIG. 3 is a schematic view of a hardware device of a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0009] FIG. 4 is a perspective view of a hardware device (e.g., nebulizer) configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0010] FIG. 5 is an exploded perspective view of the hardware device (e.g., nebulizer) of FIG. 4, in accordance with various embodiments of the present disclosure.Attorney Docket No.81073-8002.WO00

[0011] FIG. 6 is an exploded perspective view of the opposite side of the hardware device (e.g., nebulizer) of FIG.4, in accordance with various embodiments of the present disclosure.

[0012] FIG.7A is a perspective cutaway view of a hardware device (e.g., nebulizer) configured for use with a computer-implemented system for delivering and monitoring a therapeutic, in accordance with various embodiments of the present disclosure.

[0013] FIG.7B is a perspective view of the bottom of the hardware device (e.g., nebulizer) of FIG.7A, in accordance with various embodiments of the present disclosure.

[0014] FIG.8 is a perspective view of a manifold configured for incorporation into a hardware device (e.g., nebulizer) configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0015] FIG. 9 is a perspective view of a cartridge configured for use with a hardware device (e.g., nebulizer) for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0016] FIG.10 is a transparent perspective view of the cartridge of FIG.7A, in accordance with various embodiments of the present disclosure.

[0017] FIG. 11 is a perspective view of a cartridge configured for use with a hardware device (e.g., nebulizer) for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0018] FIG. 12 is a perspective cutaway view of the hardware device (e.g., nebulizer) of FIG. 7A. including a manifold and cartridge, in accordance with various embodiments of the present disclosure.

[0019] FIG. 13 is a perspective view, cutaway perspective view, and flow diagram, of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0020] FIG. 14 is a perspective view of a hardware device (e.g., nebulizer) configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.Attorney Docket No.81073-8002.WO00

[0021] FIG. 15 is a perspective view of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure.

[0022] FIG. 16 is a cutaway perspective view of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure. DETAILED DESCRIPTION

[0023] This specification and Appendix describe various exemplary aerosol delivery systems, including in a compact mobile format; software and methods for aerosol delivery, including dynamically tunable aerosol delivery; and software and methods for accurate real-time control variable monitoring- enabled broad-spectrum delivery. The disclosure, however, is not limited to these exemplary embodiments and applications or to the manner in which the exemplary embodiments and applications operate or are described herein.

[0024] Unless otherwise defined, scientific and technical terms used in connection with the present teachings described herein shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0025] Further detail is provided in the Appendix. Aerosol delivery systems are also discussed in PCT / US2022 / 022378, the entirety of which is incorporated by reference herein.

[0026] Cardiopulmonary drug delivery via aerosolization, while offering significant therapeutic advantages, has been constrained by critical limitations in existing technologies. Traditional vaporization methods suffer from thermal degradation of medicaments, compromising drug efficacy and potentially generating harmful byproducts. Nebulization, although a preferred alternative, is highly sensitive to medicament viscosity, which restricts the range of compatible drug formulations and introduces significant challenges in achieving accurate dose titration. Furthermore, substantial condensate losses during aerosol transit, coupled with the lack of precise real-time particle size and mass flow measurement, impede the reliable delivery of specific doses, particularly for drugs requiring stringent dosing control. This deficiency has precluded the effective nebulization of numerous medications that would otherwise benefit from cardiopulmonary administration. Alternative delivery methods, such as dry powder inhalers (DPIs) and propellant-based metered dose inhalers, address some of these limitations by pre-metering doses andAttorney Docket No.81073-8002.WO00 mitigating viscosity concerns. However, even these methods lack the broad-spectrum applicability necessary to fully realize the potential of cardiopulmonary drug delivery. Therefore, a critical need exists for a nebulization system that can overcome these limitations, enabling accurate, efficient, and reliable delivery of a wider range of medications, including those requiring precise dose control and high specific doses. This present disclosure addresses this need by providing a novel hardware device (e.g., nebulization device) that integrates advanced venturi flow dynamics to minimize condensate losses, a dynamic light scattering nephelometer for real-time particle size and mass flow measurement, and a processing unit that dynamically adjusts the PWM signal to the medicament actuator or nebulizing element (e.g., nebulizing mesh element) for precise dose titration and particle size control. By mitigating the challenges associated with condensate losses and inaccurate dose measurement, this present disclosure expands the applicability of nebulized drug delivery to a broader range of medications, including those with sensitive dose-variable dependence. This advancement enables the safe and effective delivery of drugs that were previously unsuitable for nebulization, thereby improving patient outcomes and broadening the therapeutic scope of cardiopulmonary drug delivery. Terms

[0027] Note that the discussion in this section relates to any and all information provided in this application, whether it be in the specification, Appendix, drawings, applications incorporated by reference, etc. Discussion herein is not meant to limit use or meaning of these terms in any way, but only to serve as providing additional details for comprehension.

[0028] Nebulizing chamber can also be referred to as, for example, a telescoping inhalation funnel, inhalation funnel, telescoping aerosol intermix chamber, and / or internal microdroplet transit region.

[0029] Vapor or microdroplet or nebulized aerosol should be understood to include any air (or gas) diluent fluidized particle containing a drug, drug combination, formulation component, admixture, or combination.

[0030] Medicament actuator can refer to a mesh style nebulizing element. Medicament actuator can also refer to any type of nebulizing element hardware capable of generating a suspended particulate aerosol in a non-thermal (non-destructive) manner. This can include, for example, jet, ultrasonic, mesh, etc.

[0031] Mixing chamber and / or manifold can be referred to as a fluidic mixing block. The fluidic mixing block can be a manifold design that permits mixing of two components along a flow path source to a chamber in direct communication with a mesh nebulizing element (as an example of one of manyAttorney Docket No.81073-8002.WO00 medicament actuator implementations), thus enabling actuation of the medicament into an fluidized aerosol. Additional optional elements that can assist in enabling an accurate treatment regimen due to accurate bolus production and delivery in real time include, for example, (1) a low flow volume manifold design; (2) a low volume mesh element supply reservoir (can be in direct contact with the nebulizing element); (3) a dynamically adjustable medicament component flow valve(s) that can allow for dynamic viscosity and component intermix ratio tuning (e.g., drug concentration). The low volume manifolding and supply reservoir can assist in limiting the adjustment lag time during dynamic operation since adjustment of critical aerosol particle properties can also include medicament supply intermix tuning, which can be delayed from taking effect until the existing material volume within the manifolding is exhausted.

[0032] Cartridge module can also be referred to as a medicament reservoir. The medicament reservoir can be provided in such a fashion to maintain a constant backpressure in a compact form factor at low cost to manufacture. Implementation of a spring or similar mechanism as a source of nearly constant backpressure energy can limit the complexity and power demands of flow control valves that enable component intermix ratio tuning.

[0033] Specific vapor density flow analyzer (also referred to as a specific vapor density flow control module) can provide a means of measurement and automated analysis of dynamic properties of the vapor generated (at source) and exiting (at sink) the "Inhalation Funnel" / "Nebulizing Chamber" (see preceding discussion of nebulizing chamber). This hardware element and workflow can assist the mobile nebulizing apparatus with accurately delivering and measuring a target drug bolus within a series comprising a treatment regimen. This can be accomplished via a photon-based transmission, emission, and / or scatter readout(s) correlated to a basis set of encoded models and encoded setpoints that can be utilized by the system to estimate specific vapor density flow rate, particle size distribution, drug concentration per particle, difference between vapor generation rate and vapor exit rate (vapor yield), as well as microdroplet decay rate. The method may be similar, in some cases, to how a dynamic light scattering system works, or a nephelometer, but optimized for accurate measurement of fluidized particle flow within the inhalation funnel volume and transit path. A longer particle flow path and funnel volume may improve the accuracy of the readout measurements due to the larger sample volume (effectively sample size). When the vapor properties are dynamically measured during a treatment regimen, software can translate, via basis set models, control values, and setpoints, a modified set of control instructions that adjust medicament cartridge flow rates, drug concentrate-diluent intermix ratios, and / or medicament actuator (Mesh element) signal waveform in order to achieve a target specific vapor density with a corresponding flow rate. In this example, a target drug bolus, pulmonary delivery efficiency, and overall treatment regimen accuracy may be achieved and verified in a mobile device never before possible. As such, a specific vapor density flow analyzer canAttorney Docket No.81073-8002.WO00 include, for example, at least one sensor in operative communication with a logic module and configured to detect at least one characteristic associated with a user’s dispensation of the medicament from the nebulizer. Discussion

[0034] Current solutions for providing a compact mobile form factor for aerosol delivery, suffer from various issues. Current solutions suffer from a having a limited range of drugs that can be deployed in a compact form factor mobile nebulized format due to, for example:

[0035] (1) “Droplet aerosol” and “air mixing volume” mixing limitations. The minimum internal mixing volume required for sufficient droplet aerosol and air diluent intermixing in a compact mobile form factor precludes deployment of a wide range of possible drugs outside a hospital or home setting.

[0036] (2) Limited nebulizer element ability to generate stable high concentration aerosols with optimized pulmonary absorption characteristics, where stability can refer to microdroplet half-life during transit, and / or emulsion stability within aerosolized microdroplets (in cases where microdroplets can comprise an emulsified oil soluble drug mixture). Aerosol particle size distribution and microdroplet drug concentration preferably can be dynamically tuned to best follow a specific vapor density target and corresponding drug bolus mass flow rate target depending on, for example, measured control variables, patient behaviors, droplet transit stability half-life, and encoded models. This medicament actuator (e.g., nebulizing element) should also optimize its signal waveform driver in order to match the variable viscosity profile of the incoming medicament mixture since drug concentration admix tuning of the incoming liquid stream is also dynamically adjusted.

[0037] (3) Limitations of existing compact mobile hardware to store one or more drug solutions, or concentrates, and a diluent. In order to enable a broad spectrum of different drugs to be deployed in a mobile aerosolized form factor, there needs to be a method of storing and controlled measured dispensing of a source of drug and diluent input fluid(s).

[0038] (4) Limitations in generating a specific aerosol density, size distribution, microdroplet drug concentration, corresponding drug mass flow rate per inhaled bolus, and overall pulmonary delivery efficiency due to the lack of existing hardware that can dynamically change drug and diluent input actuation feed ratio concentration. Corresponding drug concentration within each aerosolized microdroplet requires dynamic adjustment of medicament actuator or nebulizing element actuation waveform to match the fluid viscosity of input at variable drug c diluent intermix ratios.Attorney Docket No.81073-8002.WO00

[0039] (5) Limited capability to dynamically tune aerosol droplet size and density based on measured control variables in order to achieve and maintain specific aerosol density target, a total bolus per breath, and overall net integrated dose per medication delivery period.

[0040] (6) Limited medicament actuator (e.g., nebulizing element) capacity to non-destructively aerosolize medications, complex medication mixtures, adducts, and functional molecular motifs / structures by controlling shear forces, droplet sizes, drug and diluent intermix balance, as well as other physical constants relevant to microdroplet generation such as temperature, pressures for example.

[0041] The present disclosure discusses various features that can be used alone, or in combination, to solve these limitations.

[0042] (A) Telescoping nebulizing chamber. Telescoping vapor intermixing manifold provides access to enable an adequate “droplet aerosol” and “air mixing volume” capacity. The telescoping vapor intermixing manifold can enable accurate optical measurement of specific vapor density concentration (droplet count per unit volume), particle size distribution, aerosol flow rate, drug concentration, and droplet stability half-life. Engineered flow geometry and air diluent inputs provide for venturi enhanced droplet aerosol mixing within a compact flow path and volume.

[0043] (B) Dynamic nebulizer actuation element signal waveform turning control algorithm and variable input model.

[0044] (C) Multi-reservoir medicament storage cartridge with level and flow sense. The multi-reservoir storage cartridge can include one or more of optical, inductive, capacitive, hall, mechanical or magnetic level sense readout. The storage cartridge reservoir output flow rate can be measured via mechanical (typically MEMS), caloric, hall, optical, ultrasonic, or inductive means. The sensor output model can be flow-geometry tuned.

[0045] (D) Fluidic Mixing Block. Block an include a compact multi-reservoir output mixing manifold with variable reservoir output volume flow intermix control capability. Can further include a dynamic control variable intermix ratio tuning algorithm that can adjust drug concentration admixture composition based off, for example, specific vapor density flow analyzer / sensor output to achieve a target specific drug concentration within each microdroplet at a specific microdroplet aerosol concentration and corresponding drug mass flow rate per breath bolus.

[0046] (E) Specific vapor density flow analyzer / sensor. Can include, for example, optical measurement of specific vapor density concentration (droplet count per unit volume), particle sizeAttorney Docket No.81073-8002.WO00 distribution, aerosol flow rate, drug concentration, and / or droplet stability half-life utilizing photon transmittance, dynamic photon scattering, and / or photon absorbance for example. This feature can also enable Venturi-enhanced optical readout of microdroplet size distribution, concentration, decay rate (e.g. the rate of microdroplet condensate loss often resulting from microdroplet ripening), and velocity due to greater perpendicular component of flow streamlines with respect to optical sensing elements within manifold.

[0047] Referring now to FIGS. 2-12, the present disclosure provides a hardware device (e.g., portable nebulizer) 16. The portable nebulizer 16 includes a housing 169 defining a storage / mixing chamber 1691 and a nebulizing chamber 1692. The power source (e.g., battery) may be disposed between or parallel to (e.g., inline) the storage / mixing chamber 1691 and the nebulizing chamber 1692. The storage / mixing chamber 1691 houses a cartridge 163 and a storage portion (e.g., chamber) 1810 of a manifold 180. An exit port 170 is disposed in the housing 169 in fluid communication with the nebulizing chamber 1692 and generally opposite the storage / mixing chamber 1691.

[0048] In various embodiments, a portion of the nebulizing chamber 1692 serves as an integrated storage / mixing chamber 1691 and is configured to mix (e.g., dilute) concentrated vapor generated at the medicament actuator 1832 with air or other diluent before the diluted vapor exits the exit port 170. In various embodiments, a single chamber in a device 16 can serve as both the nebulizing chamber 1692 and storage / mixing chamber 1691. In various embodiments, a single chamber in a device 16 can serve as both the nebulizing chamber 1692 and storage / mixing chamber 1691, such that the function of a nebulizing chamber and a storage / mixing chamber is accomplished by the same, single, chamber.

[0049] The cartridge 163 can include one or more medicament reservoirs (exemplified by features 1631a-c); at least one of the reservoirs (e.g., 1631a, b and / or c) includes a medicament. In various embodiments, the cartridge 163 includes more than one medicament reservoirs, each configured to store a medicament. If the medicament is in a concentrated form, at least one other reservoir 1631b-c may include a medicament vehicle for diluting the concentrated medicament before administration to the user. In various embodiments, the cartridge 163 is replaceable. In various embodiments, the cartridge 163 is not readily removable from the housing 169.

[0050] The nebulizing chamber 1692 can be in fluid communication with the at least one medicament reservoir (e.g., 1631a-c) and can include a medicament actuator-embedded (e.g., nebulizing mesh- embedded) manifold 1830 configured to mix a portion of the medicament with a medicament vehicle and / or with other medicament or diluent before reaching a medicament actuator(s) 1832 embedded in the surfaceAttorney Docket No.81073-8002.WO00 of the medicament actuator-embedded (e.g., nebulizing mesh-embedded) manifold 1830. The medicament actuator(s) 1832 of the nebulizing chamber 1692 can also include, or be in the form of, one or more nebulizing mesh elements (e.g., piezo element(s)) in electrical communication with a power source 162 via electrical contacts (not shown for clarity), and can be configured to vaporize (e.g., nebulize) the medicament to form a medicament vapor that emanates from a top 1835 of the manifold 180. In various embodiments, the one or more medicament actuators 1832 (e.g., nebulizer mesh elements or vaporizer heating elements / ultrasonic elements) is oriented orthogonal or substantially orthogonal (e.g., such that the faces of the actuator(s) are antiparallel, orthogonal, or substantially orthogonal to a direction of travel 1840) to the direction 1840 of travel of the one or more medicament from the storage chamber 1810 to the medicament actuator(s) 1832 to the exit port 1835 of the manifold 180.

[0051] A logic / compute module 166 within the nebulizer 16 is configured to enable the nebulizer 16 to receive data from and send data to a remote software environment 12. The remote software environment 12 may include instructions that, when queried by the logic / compute module 166, limit use of the nebulizer (e.g., prevents the power source from energizing the medicament actuator(s) 1832, e.g., nebulizer mesh or vaporizer heating element / ultrasonic plate) if one or more use conditions are not satisfied.

[0052] In various embodiments, the nebulizer 16 additionally includes a hardware network module 161 in operative communication with the logic / compute module 166 and configured to enable two-way data communication between the nebulizer 16 and the remote software module 12.

[0053] In various embodiments, the nebulizer 16 additionally includes a hardware security module 164 in operative communication with the logic / compute module 166 and configured to prevent unauthorized dispensing of the medicament from the nebulizer 16.

[0054] In various embodiments, the nebulizer 16 additionally includes at least one sensor 168 in operative communication with the logic / compute module 166 and configured to detect at least one characteristic associated with a user’s dispensation of the medicament from the nebulizer 16. In various embodiments, the sensor 168 is one or more of: a sensor for assessing a density of vapor emanating from the medicament actuator (e.g., nebulizing mesh) 1832 (e.g., a laser particle sensor or ionization type sensor), a flow sensor for assessing an amount of vapor inhaled by a user through the exit port (e.g., a pressure sensor or volumetric flow sensor), a flow sensor for assessing an amount of the medicament withdrawn from the cartridge (e.g., a fluid flow sensor), a position sensor for assessing a change in position of a float or plunger associated with a volume of the medicament, and a pH sensor for assessing a pH level of vapor emanating from the medicament actuator (e.g., nebulizing mesh).Attorney Docket No.81073-8002.WO00

[0055] In various embodiments, the logic / compute module 166 is configured to control power provided to the medicament actuator (e.g., nebulizing mesh) or a vaporizer heating element / ultrasonic plate 1820 from the power source in response to calibration data received from the remote software environment 12.

[0056] In various embodiments, the logic / compute module 166 is configured to control power provided to the medicament actuator (e.g., nebulizing mesh) or vaporizer heating element / ultrasonic plate 1820 from the power source in response to calibration data received from the remote software environment 12 and in response to information obtained from the one or more sensors 168.

[0057] In various embodiments, the logic / compute module 166 is configured to cause the hardware security module 164 to prevent power from flowing from the power source to the medicament actuator (e.g., nebulizing mesh) or vaporizer ultrasonic plate 1820 in response to security information received from the remote software environment 12. In various embodiments, the security information includes information associated with an authorized frequency of medicament dispensation.

[0058] In various embodiments, the logic / compute module 166 is configured to receive information obtained from the at least one sensor 168. In various embodiments, the logic / compute module 166 is further configured to transmit the information obtained from the at least one sensor 168 to the remote software environment 12.

[0059] Referring now to FIG. 13, illustrated is a perspective view (A), cutaway perspective view (B), and flow diagram (C), of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure. In an extended (e.g., telescoping) configuration, as illustrated in FIG. 13, a hardware device 16 (e.g., nebulizer) is shown, in which the upper (extendable) portion or housing 1310 is configured to extend (about a static portion or housing 1340) to provide a greater internal volume within the interior of the housing 169, so that the air intakes 1639, located in specifically optimized locations along the sidewall of the housing 169, allow laminar flow 1322 of microdroplet aerosol diluent (e.g., air) into the storage / mixing chamber 1691 at a vector substantially perpendicular to the net flow direction of the vapor stream, thereby maintaining a laminar separation gap of incoming aerosol diluent between microdroplet containing aerosol and the internal sidewall of the housing 169, to aid in minimizing condensate loss of medicament along the flow path, and, by reinforcing the central column aerosol vortex within the venturi region, to further confine the aerosol to the center of the flow path and away from the sidewalls, thus further limiting condensate loss.Attorney Docket No.81073-8002.WO00

[0060] In various embodiments the outer housing portion serves the purpose of protecting certain components from damage when not in use and may be retracted from an initial position in order to enable access to specific interfacing component or features (e.g. buttons, mouthpiece opening (170), etc.). In various embodiments, the outer housing portion may be retracted from an initial position to reduce the internal flow path and internal volume of the housing 169 depending on specific characteristics of the aerosol (e.g. size distribution, concentration, decay rate, etc.).

[0061] Regarding air intake 1639, in various embodiments, the air intake gap 1639 can be disposed between the housing 1630 of the cartridge module 163 and the housing 169 of the hardware device 16. When present, the air intake gap 1639 enables air to be drawn into the interior of the hardware device 16 (e.g., into the storage / mixing chamber 1691). In various embodiments, the air intake gap 1639 has an aperture of about 50 pm to about 500 pm, about 100 pm to about 400 pm, or about 200 pm to about 300 pm, for example about 50 pm, about 60 pm, about 70 pm, about 80 pm, about 90 pm, about 100 pm, about 110 pm, about 120 pm, about 130 pm, about 140 pm, about 150 pm, about 160 pm, about 170 pm, about 180 pm, about 190 pm, about 200 pm, about 210 pm, about 220 pm, about 230 pm, about 240 pm, about 250 pm, about 260 pm, about 270 pm, about 280 pm, about 290 pm, about 300 pm, about 310 pm, about 320 pm, about 330 pm, about 340 pm, about 350 pm, about 360 pm, about 370 pm, about 380 pm, about 390 pm, about 400 pm, about 410 pm, about 420 pm, about 430 pm, about 440 pm, about 450 pm, about 460 pm, about 470 pm, about 480 pm, about 490 pm, or about 500 pm. In various embodiments, the air intake gap 1639 is disposed on a side wall of the housing 169 (see, e.g., FIGS. 13 and 15). In various embodiments, the air intake gap 1639 is disposed on a bottom surface of the housing 169 (see, e.g., FIGS. 7A-7B, 12).

[0062] Cutaway view (B) of FIG.13 illustrates hardware device 16 comprising a control surface 1636 (e.g., fins), flow vectoring 1320, and resulting turbulent venturi mixing (in turbulent venturi mixing zone 1637) along the extended flow path volume provided by the telescoping feature of device 16. Specifically, flow vectoring 1320, initiated by control surface 1636, imparts a tangential velocity component to the incoming aerosol flow, creating a circular vortex vectoring of aerosol flow. This circular vectoring occurs in a lower laminar flow zone, where the flow is initially organized and predictable. As the aerosol flow progresses upward within the extended flow path volume, it enters a turbulent transition region. In this region, the kinetic energy of the rotating flow is converted into turbulent kinetic energy. Finally, the flow transitions into the upper turbulent venturi mixing zone 1637, where the established vortex evolves into a venturi effect. This venturi effect is reinforced by the net pressure drop along the extended flow path volume, from the air inlets to the user's suction point, which maintains and strengthens the vortex. Thus, the flow vectoring 1320 at the bottom of the chamber initiates the circular vectoring, which, in conjunctionAttorney Docket No.81073-8002.WO00 with the macro pressure drop occurring along the length of the extended flow path volume, enables the formation and reinforcement of the venturi mixing at the top. Also refer to flow diagram (C) for a separate illustration of the flow vectoring, laminar flow zone, turbulent transition region and turbulent venturi mixing zone.

[0063] Referring now to FIG. 14, illustrated is a perspective view of a hardware device 16 (e.g., nebulizer) configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure. As discussed above, in various embodiments, the nebulizer 16 can include at least one sensor 168 in operative communication with the logic / compute module 166 and configured to detect at least one characteristic associated with a user’s dispensation of the medicament from the nebulizer 16. In various embodiments, the sensor 168 is one or more of: a sensor for assessing a density of vapor emanating from the medicament actuator (e.g., nebulizing mesh) 1832 (e.g., a laser particle sensor or ionization type sensor), a flow sensor for assessing an amount of vapor inhaled by a user through exit port 170 (e.g., a pressure sensor or volumetric flow sensor), a flow sensor for assessing an amount of the medicament withdrawn from the cartridge (e.g., a fluid flow sensor), a position sensor for assessing a change in position of a float or plunger associated with a volume of the medicament, and a pH sensor for assessing a pH level of vapor emanating from the medicament actuator (e.g., nebulizing mesh). FIG.14 illustrates, in particular, an optical particle sensor (e.g., a laser particle sensor) or ionization type sensor 168, serving within the capacity of a nephelometer, for assessing the particle size distribution and concentration of the aerosol or vapor emanating from the medicament actuator (e.g., nebulizing mesh), wherein the ionization type sensor 168 may also be used to sense the concentration of active drug component within the aerosol microdroplets.

[0064] Referring now to FIG.15, illustrated is a perspective view of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure. In particular, A illustrates device 16 in a closed configuration. In various embodiments, the closed configuration is an inactive configuration. B illustrates device 16 in an open configuration. In various embodiments, the open configuration is an active configuration.

[0065] Referring now to FIG.16, illustrated is a cutaway perspective view of a hardware device (e.g., nebulizer), with telescoping feature, configured for use with a computer-implemented system for delivering and monitoring a therapeutic regimen, in accordance with various embodiments of the present disclosure. In particular, FIG. 16 illustrates control surface(s) 1636 proximate a medicament actuator or nebulizing actuating element 1832 (e.g. a nebulizing mesh). In various embodiments, control surface(s)1636 areAttorney Docket No.81073-8002.WO00 adjacent the medicament actuator or nebulizing actuating element 1832. In various embodiments, control surface(s) 1636 and medicament actuator or nebulizing actuating element 1832 are below storage / mixing chamber 1691. In various embodiments, control surface(s) 1636 and medicament actuator or nebulizing actuating element are provided with sufficient geometry to generate a turbulent venturi mixing zone 1637. Computer Implemented System

[0066] In various embodiments, the embodiments disclosed herein, which are generally directed towards systems, software and methods for aerosol delivery, including dynamically tunable aerosol delivery, and including accurate real-time control variable monitoring-enabled broad-spectrum delivery, can be implemented via computer software or hardware. Refer to the Appendix for further information regarding the system, devices and methods provided herein, in accordance with various embodiments.

[0067] FIG. 1 (see Appendix) is a block diagram illustrating a computer system 100 upon which embodiments of the present teachings may be implemented. In various embodiments of the present teachings, computer system 100 can include a bus 102 or other communication mechanism for communicating information and a processor 104 coupled with bus 102 for processing information. In various embodiments, computer system 100 can also include a memory, which can be a random-access memory (RAM) 106 or other dynamic storage device, coupled to bus 102 for determining instructions to be executed by processor 104. Memory can also be used for storing temporary variables or other intermediate information during execution of instructions to be executed by processor 104. In various embodiments, computer system 100 can further include a read only memory (ROM) 108 or other static storage device coupled to bus 102 for storing static information and instructions for processor 104. A storage device 110, such as a magnetic disk or optical disk, can be provided and coupled to bus 102 for storing information and instructions.

[0068] In various embodiments, computer system 100 can be coupled via bus 102 to a display 112, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 114, including alphanumeric and other keys, can be coupled to bus 102 for communication of information and command selections to processor 104. Another type of user input device is a cursor control 116, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 104 and for controlling cursor movement on display 112. This input device 114 typically has two degrees of freedom in two axes, a first axis (i.e., x) and a secondAttorney Docket No.81073-8002.WO00 axis (i.e., y), that allows the device to specify positions in a plane. However, it should be understood that input devices 114 allowing for 3-dimensional (x, y and z) cursor movement are also contemplated herein.

[0069] Consistent with certain implementations of the present teachings, results can be provided by computer system 100 in response to processor 104 executing one or more sequences of one or more instructions contained in memory 106. Such instructions can be read into memory 106 from another computer-readable medium or computer-readable storage medium, such as storage device 110. Execution of the sequences of instructions contained in memory 106 can cause processor 104 to perform the processes described herein. Alternatively, hard-wired circuitry can be used in place of or in combination with software instructions to implement the present teachings. Thus, implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.

[0070] The term “computer-readable medium” (e.g., data store, data storage, etc.) or “computer- readable storage medium” as used herein refers to any media that participates in providing instructions to processor 104 for execution. Such a medium can take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Examples of non-volatile media can include, but are not limited to, dynamic memory, such as memory 106. Examples of transmission media can include, but are not limited to, coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 102.

[0071] Common forms of computer-readable media include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, any other optical medium, punch cards, paper tape, any other physical medium with patterns of holes, a RAM, PROM, and EPROM, a FLASH-EPROM, another memory chip or cartridge, or any other tangible medium from which a computer can read.

[0072] In addition to computer-readable medium, instructions or data can be provided as signals on transmission media included in a communications apparatus or system to provide sequences of one or more instructions to processor 104 of computer system 100 for execution. For example, a communication apparatus may include a transceiver having signals indicative of instructions and data. The instructions and data are configured to cause one or more processors to implement the functions outlined in the disclosure herein. Representative examples of data communications transmission connections can include, but are not limited to, telephone modem connections, wide area networks (WAN), local area networks (LAN), infrared data connections, NFC connections, etc.Attorney Docket No.81073-8002.WO00

[0073] It should be appreciated that the methodologies described herein, flow charts, diagrams and accompanying disclosure can be implemented using computer system 100 as a standalone device or on a distributed network or shared computer processing resources such as a cloud computing network.

[0074] The methodologies described herein may be implemented by various means depending upon the application. For example, these methodologies may be implemented in hardware, firmware, software, or any combination thereof. For a hardware implementation, the processing unit may be implemented within one or more application specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), programmable logic devices (PLDs), field programmable gate arrays (FPGAs), processors, controllers, micro-controllers, microprocessors, electronic devices, other electronic units designed to perform the functions described herein, or a combination thereof.

[0075] In various embodiments, the methods of the present teachings may be implemented as firmware and / or a software program and applications written in conventional programming languages such as C, C++, Python, etc. If implemented as firmware and / or software, the embodiments described herein can be implemented on a non-transitory computer-readable medium in which a program is stored for causing a computer to perform the methods described above. It should be understood that the various engines described herein can be provided on a computer system, such as computer system 100, whereby processor 104 would execute the analyses and determinations provided by these engines, subject to instructions provided by any one of, or a combination of, memory components 106 / 108 / 110 and user input provided via input device 114.

[0076] In describing the various embodiments, the specification may have presented a method and / or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and / or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments. Similarly, any of the various system embodiments may have been presented as a group of particular components. However, these systems should not be limited to the particular set of components, now their specific configuration, communication and physical orientation with respect to each other. One skilled in the art should readily appreciate that these components can have various configurations andAttorney Docket No.81073-8002.WO00 physical orientations (e.g., wholly separate components, units and subunits of groups of components, different communication regimes between components).

[0077] Although specific embodiments and applications of the disclosure have been described in this specification, these embodiments and applications are exemplary only, and many variations are possible. Exemplary Embodiments

[0078] Embodiment 1: A hardware device for therapeutic administration of a medicament, comprising a housing comprising an internal volume.

[0079] Embodiment 2: The hardware device of Embodiment 1, the housing further comprising a static portion and a mobile portion; wherein the static portion and mobile portion form a first internal volume when in an inactive position, wherein the static portion and mobile portion form a second internal volume when in an active position, and wherein the mobile portion is configured and arranged to move about the static portion to form the second internal volume when in the active position.

[0080] Embodiment 3: The hardware device of Embodiment 2, wherein the second internal volume is greater than the first internal volume.

[0081] Embodiment 4: The hardware device of Embodiment 2, wherein the second internal volume is less than the first internal volume.

[0082] Embodiment 5: The hardware device of Embodiments 1 to 4, wherein the housing further comprises air intake regions enabling air to be drawn into the interior of the hardware device.

[0083] Embodiment 6: The hardware device of Embodiment 5, wherein the air intake regions enable the generation of a laminar flow of air diluent in the internal volume of the housing.

[0084] Embodiment 7: The hardware device of Embodiments 5 and 6, wherein the air intake regions extend laterally along the housing, and optionally enable the generation of a laminar flow of air diluent in the internal volume.

[0085] Embodiment 8: The hardware device of Embodiments 5 to 7, wherein the air intake regions extend longitudinally along the housing, and optionally enable the generation of a laminar flow of air diluent in the internal volume.Attorney Docket No.81073-8002.WO00

[0086] Embodiment 9: The hardware device of Embodiments 1 and 2, further comprising a storage / mixing chamber.

[0087] Embodiment 10: The hardware device of Embodiment 9, wherein the storage / mixing chamber is configured and arranged to mix an air volume having a concentrated medicament microdroplet population per unit volume with air as a diluent of those microdroplets within the volume flow, thereby decreasing the microdroplet per air volume density.

[0088] Embodiment 11: The hardware device of Embodiments 9 and 10, the storage / mixing chamber further comprising one or more fluid control surfaces geometrically configured and arranged to generate a turbulent venturi mixing zone of medicament microdroplets and air diluent.

[0089] Embodiment 12: The hardware device of Embodiments 9 to 11, the storage / mixing chamber further comprising one or more fluid control surfaces and a medicament actuator, geometrically configured and arranged to generate a turbulent venturi mixing zone of medicament microdroplets and air diluent.

[0090] Embodiment 13: The hardware device of Embodiments 1 and 2, further comprising an optical sensor.

[0091] Embodiment 14: The hardware device of Embodiment 13, wherein the optical sensor is configured and arranged to measure at least one of: droplet size distribution, droplet concentration per unit volume, dynamic droplet flow rate, and medicament concentration within each droplet.

[0092] Embodiment 15: The hardware device of Embodiments 13 and 14, the housing further comprising a venturi mixing zone configured and arranged to provide a controlled sampling volume for the optical sensor.

[0093] Embodiment 16: The hardware device of Embodiments 1 and 2, further comprising a logic / compute module.

[0094] Embodiment 17: The hardware device of Embodiments 1 and 2, further comprising a logic / compute module configured and arranged to calculate a condensate loss rate based on measurements from the optical sensor and one or more additional sensors.

[0095] Embodiment 18: The hardware device of Embodiments 16 and 17, wherein the logic / compute module controls a power module to adjust the pulse cycle signal power to the medicament actuator to compensate for the calculated condensate loss rate.Attorney Docket No.81073-8002.WO00

[0096] Embodiment 19: The hardware device of Embodiments 1 and 2, further comprising a at least one reservoir.

[0097] Embodiment 20: The hardware device of Embodiment 19, further comprising a cartridge module comprising a medicament vehicle module component, the component comprising the at least one reservoir for mixing medicament with a suitable liquid medicament vehicle or diluent.

[0098] Embodiment 21: The hardware device of Embodiments 19 and 20, further comprising a plurality of reservoirs.

[0099] Embodiment 22: The hardware device of Embodiment 21, further comprising a cartridge module comprising a medicament vehicle module component, the component comprising the plurality of reservoirs for mixing medicament with a suitable liquid medicament vehicle or diluent.

[0100] Embodiment 23: A hardware device for therapeutic administration of a medicament, comprising: a storage / mixing chamber configured to mix an air volume having a concentrated medicament microdroplet population per unit volume with air as a diluent of those microdroplets within the volume flow, thereby decreasing the microdroplet per air volume density.

[0101] Embodiment 24: The hardware device of Embodiment 23, wherein the storage / mixing chamber (1691) includes a radially arranged plurality of fluid control surfaces (1636) with sufficient geometry to generate a turbulent venturi mixing zone (1637) of medicament microdroplets and air diluent.

[0102] Embodiment 25: A hardware device for therapeutic administration of a medicament, comprising: a power module configured to control a rate of medicament actuation and resulting medicament per unit dose dispense rate based on logic / compute module instruction by adjusting a pulse cycle signal power to a medicament actuator.

[0103] Embodiment 26: A hardware device for therapeutic administration of a medicament, comprising: a multichamber storage reservoir for multiple different medicaments and / or diluents / excipients or placebos.

[0104] Embodiment 27: The hardware device of Embodiments 23 and 24, further comprising: air intakes of specific sizes located in specifically optimized locations along a sidewall and / or a bottom surface of a housing that allow laminar flow of microdroplet aerosol diluent (air) intake into the storage / mixing chamber, thereby maintaining a laminar separation gap between microdroplet aerosol and an internal sidewall of the housing during use.Attorney Docket No.81073-8002.WO00

[0105] Embodiment 28: The hardware device of Embodiment 25, further comprising more than one medicament actuator, wherein the power module is configured and independently in communication with each independent medicament actuator, thereby allowing for ratiometric microdroplet intermixing control of different medicament aerosol streams.

[0106] Embodiment 29: The hardware device of Embodiments 23 to 26, further comprising: a cartridge module having a medicament vehicle module component comprising at least one reservoir for mixing medicament with a suitable liquid medicament vehicle or diluent.

[0107] Embodiment 30: A hardware device for therapeutic administration of a medicament, comprising: a vapor flow sensor capable of determining a flow rate and / or aerosol microdroplet concentration emanating from an exit port.

[0108] Embodiment 31: A hardware device for therapeutic administration of a medicament, comprising: a pressure sensor configured to determine a difference and change in pressure between an interior of the device and an exterior environment.

[0109] Embodiment 32: A hardware device for therapeutic administration of a medicament, comprising: a logic / compute module configured to determine / calculate a specific dose and / or total dose of medicament delivered to a patient based off of input measurements of vapor stream density, vapor flow rate, and medicament cartridge reservoir level.

[0110] Embodiment 33: The hardware device of Embodiments 23 to 32, further comprising: one or more sensors disposed proximally to a medicament actuator on an interior surface of the housing configured to assess a concentration of medicament formed by one or more actuating elements.

[0111] Embodiment 34: A hardware device for therapeutic administration of a medicament, comprising: at least one sensor; the at least one sensor in operative communication with a logic / compute module; the at least one sensor configured to detect at least one characteristic associated with a user’s dispensation of the medicament from the nebulizer; wherein the sensor is one or more of: a sensor for assessing a density of vapor emanating from a nebulizing mesh (e.g., a laser particle sensor or ionization type sensor); a flow sensor for assessing an amount of vapor inhaled by a user through the exit port (e.g., a pressure sensor or volumetric flow sensor); a flow sensor for assessing an amount of the medicament withdrawn from the cartridge (e.g., a fluid flow sensor); a position sensor for assessing a change in position of a float or plunger associated with a volume of the medicament, and a pH sensor for assessing a pH level of vapor emanating from the nebulizing mesh.Attorney Docket No.81073-8002.WO00

[0112] Embodiment 35: The hardware device of Embodiment 35, wherein: the logic / compute module is configured to control power provided to the nebulizer mesh or vaporizer heating element / ultrasonic plate from the power source in response to calibration data received from a remote software environment; and / or the logic / compute module is configured to control power provided to the nebulizer mesh or vaporizer heating element / ultrasonic plate from the power source in response to calibration data received from the remote software environment and in response to information obtained from the one or more sensors.

Claims

Attorney Docket No.81073-8002.WO00 CLAIMS 1. A hardware device for therapeutic administration of a medicament, comprising: a housing comprising an internal volume.

2. The hardware device of Claim 1, the housing further comprising a static portion and a mobile portion; wherein the static portion and mobile portion form a first internal volume when in an inactive position, wherein the static portion and mobile portion form a second internal volume when in an active position, and wherein the mobile portion is configured and arranged to move about the static portion to form the second internal volume when in the active position.

3. The hardware device of Claim 2, wherein the second internal volume is greater than the first internal volume.

4. The hardware device of Claim 2, wherein the second internal volume is less than the first internal volume.

5. The hardware device of Claim 2, wherein the housing further comprises air intake regions enabling air to be drawn into the interior of the hardware device.

6. The hardware device of Claim 5, wherein the air intake regions enable the generation of a laminar flow of air diluent in the internal volume of the housing.

7. The hardware device of Claim 5, wherein the air intake regions extend laterally along the housing, and optionally enable the generation of a laminar flow of air diluent in the internal volume.

8. The hardware device of Claim 5, wherein the air intake regions extend longitudinally along the housing, and optionally enable the generation of a laminar flow of air diluent in the internal volume.

9. The hardware device of Claim 2, further comprising a storage / mixing chamber.

10. The hardware device of Claim 9, wherein the storage / mixing chamber is configured and arranged to mix an air volume having a concentrated medicament microdroplet population per unit volume with air as a diluent of those microdroplets within the volume flow, thereby decreasing the microdroplet per air volume density.

11. The hardware device of Claim 9, the storage / mixing chamber further comprising one or more fluid control surfaces geometrically configured and arranged to generate a turbulent venturi mixing zone of medicament microdroplets and air diluent.Attorney Docket No.81073-8002.WO00 12. The hardware device of Claim 9, the storage / mixing chamber further comprising one or more fluid control surfaces and a medicament actuator, geometrically configured and arranged to generate a turbulent venturi mixing zone of medicament microdroplets and air diluent.

13. The hardware device of Claim 2, further comprising an optical sensor.

14. The hardware device of Claim 13, wherein the optical sensor is configured and arranged to measure at least one of: droplet size distribution, droplet concentration per unit volume, dynamic droplet flow rate, and medicament concentration within each droplet.

15. The hardware device of Claim 14, the housing further comprising a venturi mixing zone configured and arranged to provide a controlled sampling volume for the optical sensor.

16. The hardware device of Claim 2, further comprising a logic / compute module.

17. The hardware device of Claim 2, further comprising a logic / compute module configured and arranged to calculate a condensate loss rate based on measurements from the optical sensor and one or more additional sensors.

18. The hardware device of Claim 16, wherein the logic / compute module controls a power module to adjust the pulse cycle signal power to the medicament actuator to compensate for the calculated condensate loss rate.

19. The hardware device of Claim 2, further comprising a at least one reservoir.

20. The hardware device of Claim 19, further comprising a cartridge module comprising a medicament vehicle module component, the component comprising the at least one reservoir for mixing medicament with a suitable liquid medicament vehicle or diluent.

21. The hardware device of Claim 19, further comprising a plurality of reservoirs.

22. The hardware device of Claim 21, further comprising a cartridge module comprising a medicament vehicle module component, the component comprising the plurality of reservoirs for mixing medicament with a suitable liquid medicament vehicle or diluent.

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