Patent Description:
There are various devices currently available for delivering drugs to the nasal cavity. Examples of prior art intranasal delivery devices include: <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>. <CIT> relates to a nasal delivery device for and a method of delivering a substance, in particular one of a liquid, as a suspension or solution, or a powder containing a medicament, especially systemic or topical pharmaceuticals, or a vaccine to the nasal airway of a subject.

The inventors have determined a need for improved intranasal delivery devices.

In accordance with an aspect, there is provided an intranasal drug delivery device having compliant or flexible, soft nib to precisely locate the dosage and provide comfort for user. The term drug can also be used herein to refer to other agents such as vitamins, fragrance, saline or non-pharmaceutical agents.

In accordance with an aspect, there is provided an intranasal drug delivery device having a cocking mechanism and actuator to load and release dosage.

In accordance with an aspect, there is provided an intranasal drug delivery device having a non-air interface mechanically pressurized fluid reservoir to enable dosing independent of orientation and to load shot chamber. In some example embodiments, reservoir can be collapsible from external pressure, including ambient air pressure.

In accordance with an aspect, there is provided an intranasal drug delivery device connectable to a facial or device recognition application to prevent intentional or unintentional misuse.

In accordance with an aspect, there is provided an intranasal fluid delivery device comprising a dispensing tip connected to a hollow needle, a shot chamber carrying a fluid, the shot chamber having a diaphragm at one end and a plunger at the other end, and an actuator connected to a push rod moveable toward the shot chamber and having a locking mechanism, wherein pushing the actuator releases the locking mechanism, allowing the push rod to push against the plunger, exerting pressure on the fluid and forces the needle through the diaphragm into the shot chamber such that the fluid flows out of the needle into the dispensing tip.

In accordance with an aspect, there is provided an apparatus for delivering fluid to a nasal volume comprising a housing having a first end with a dispensing opening and a second end with an actuating opening, a dispensing tip coupled to the dispensing opening, a capsule within the housing between the actuating opening and the dispensing opening, the capsule comprising a tube pre-filled with fluid between a diaphragm and a plunger, and, an actuator coupled to the actuating opening, the actuator comprising a push rod moveable into contact with the plunger and held back by a locking mechanism, and a spring urging the push rod toward the plunger.

Also disclosed is a method for targeted intranasal fluid delivery. The method comprises inserting a compliant dispensing tip into a nasal cavity, and ejecting a fluid from the compliant dispensing tip to deliver a laminar liquid bolus to a targeted region within the nasal cavity. The targeted region may be an olfactory region of the nasal cavity. Inserting the compliant dispensing tip into the nasal cavity may comprise inserting the compliant dispensing tip into the nasal cavity may comprise positioning an end of the compliant dispensing tip proximate to the olfactory region. The compliant dispensing tip may comprise a cannula. Ejecting the fluid may comprise ejecting the fluid with a controlled velocity profile to limit shear forces on the fluid.

In various further aspects, the disclosure provides corresponding systems and devices, and logic structures such as machine-executable coded instruction sets for implementing such systems, devices, and methods.

In this respect, before explaining at least one embodiment in detail, it is to be understood that the embodiments are not limited in application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

Many further features and combinations thereof concerning embodiments described herein will appear to those skilled in the art following a reading of the instant disclosure.

Embodiments of methods, systems, and apparatus are described through reference to the drawings.

Currently disposable intranasal drug delivery devices are characterized by low accuracy/uniformity of drug dosing, no design for anatomic variability and poor design for human factors - efficacy and safety. The applications where these shortcomings are most detrimental are: direct-to-brain delivery path (uptake through olfactory epithelium into CSF, action in brain), systemically acting drugs (uptake through mucosa into vasculature, systemic action), vaccines (uptake and action in mucosa), and topically acting drugs (uptake and action in mucosa).

The following provides for intranasal delivery of new and existing drugs, with the following benefits: less cost, increased effectiveness, increased safety (both to patient and society), and increased convenience (in terms of health care).

The following provides for opportunities in terms of design for markets where access to health care is challenged (humanitarian impact) and in terms of design for prevention of drug misuse.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments.

The device <NUM> has a compliant or flexible, soft nib <NUM> (as opposed to a hard nib) to precisely locate the dosage. The soft nib <NUM> also provides comfort for user and may minimize blocking by the nasal wall or congestion.

Septal deviation can cause different health related problems. In some embodiments compliant, soft nib <NUM> conforms to the anterior aspect of the intranasal passage. In some embodiments the soft nib <NUM> is biased to follow the patient's septum. This allows the tip <NUM> to be placed in a location in the nasal cavity to discharge medicine targeting the olfactory region and accommodates differences in nasal cavity anatomy.

In some embodiments compliant, soft nib <NUM> has a kiss-cut valve near the tip <NUM>. The valve reduces the partial discharge at the front and backend of the actuation. The tip <NUM> also reduces or eliminates air or contaminates from contacting the line-fill remaining in the nozzle between dosing. In some embodiments the orientation of the kiss cut is off set from the end of the tip <NUM> for directing the medicine in the direction of the olfactory region of the nasal anatomy. The nib <NUM> can be a multiple material over-moulded nib in some embodiments. As shown in <FIG>, in some embodiments the nib may have a bulbous or ball shaped end portion <NUM> to ease the insertion and facilitate better laminar flow along the nasal ridge. As shown in <FIG>, in some embodiments, the compliant nib utilizes an 'alpha loop' <NUM> to facilitate positioning an end of the dispensing tip past an obstruction. One of the tricks in interventional cardiology to pass a guidewire past a stricture or calcified obstruction is to force the flexible tip guide wire into the obstruction. The tip will naturally bend back on itself and the wire finds its way through the obstruction with the alpha loop leading. The larger bearing surface helps to steer the wire to the point of least resistance and it will slip through the stricture/obstruction. This embodiment may be utilized in trauma where a nose may be less than perfect, this could be the shape that would help the compliant nib find its mark.

The device <NUM> has an actuator <NUM> (e.g. button, trigger) and cocking mechanism <NUM> to release dosage that is reproducible to reduce human error/variation. Use of a cock-and-release mechanism in some embodiments promotes steady positioning during delivery and reduces the need for priming of the device <NUM>, thereby reducing the possibility of operator error. In some embodiments a finger press button actuation discharges the shot chamber. This method of actuating the device <NUM> requires very little dexterity or fine motor skills which may be of particular importance to patients whose motor skills may be impaired e.g. patients with Parkinson's. Priming can refer to ensuring full liquid filling dosing/metering mechanism is suitable for pumping of the liquid including but not limited to positive displacement pumping.

The device <NUM> has an internal reservoir that can be under pressure constantly in some embodiments to enable dosing independent of orientation (e.g. the user can be standing up or laying down and it will work). The reservoir may be a bag and may be collapsible by external pressure, including ambient air pressure. The pressure within the reservoir may change depending on the spring used, but it can always be under some amount of pressure.

In some embodiments the device <NUM> has no air-port for filling, storing or actuating the device <NUM>. This allows for traveling or transport by air, particularly unpressurized aircraft or higher elevations and may be useful for oxygen sensitive medicine and extending shelf life of certain medicines, particularly where there is no cold-chain infrastructure. In addition, this makes the device difficult to tamper with. In some embodiments, there can be an air bleed port.

In some embodiments the shape of the device <NUM> allows for correct nozzle positioning and ergonomic grip that does not engage the shoulder, wrist, or any part of the other arm not activating the device <NUM>. The design of device <NUM> promotes minimal use of shoulder and arm movement.

In some embodiments the design of device <NUM> is made highly ergonomic in form, taking inspiration both from a wider remote controller design and a more dexterous pen design.

The ergonomics and considered human factors create a step change in the state of the art for nasal delivery devices. The design minimizes human error, allowing for a targeted, repeatable, and metered dose delivery. The design accommodates a consumable drug reservoir for short to long term use, while allowing for a low cost single patient consumable. This gives the ability for a wide variety of drugs to be filled at the point of care or by pharmaceutical filling lines. The design allows for, as an example, a compliant, soft nib <NUM> with an ultra-soft, matte finish, elastomeric shroud.

The compliant, soft nib <NUM> of the device is entered into the intranasal cavity and uses the common internal nasal geometry to guide the tip proximate to the olfactory region. The compliant soft nib <NUM> stops at a distance from the olfactory region and the ejected drug bolus is guided to the olfactory by the native geometry of the nasal anatomy. The device mechanism supports a pocketable form being based on compact and low-cost injection-mouldable parts.

<FIG> shows an example intranasal drug delivery device <NUM> with a lid <NUM> or cap according to some embodiments.

In some embodiments the lid <NUM> may be used with the cocking mechanism <NUM>, or instead of cocking mechanism <NUM>, as part of reloading the intranasal drug delivery device <NUM>. The addition of the lid <NUM> increases the grip size of the drug delivery device <NUM> and prevents misfiring of the drug delivery device <NUM>. In some embodiments lid <NUM> may provide extra space for full hand grip when attached to bottom of device <NUM>. In some embodiments lid <NUM> is shaped to increase the surface area without obstruction by hand when in use so that machine readable indicia (i.e. URL code) can be added to the increased surface area.

In some embodiments, the device <NUM> may include rechargeable energy storage to provide motive energy with separate actuation. Rechargeable energy may include electrical, chemical or pressurized fluid storage.

<FIG> shows an illustration of the nasal cavity <NUM> including the olfactory region <NUM>, upper nares <NUM> and lower nares <NUM>.

In topical drug delivery, drug is delivered to the entire mucosa, i.e. both the upper nares <NUM> and lower nares <NUM>. In systematic drug delivery, drug is delivered through the mucosa of the upper nares <NUM> into the vasculature. In direct-to-brain drug delivery, drug is delivered mainly through the olfactory region <NUM> diffusion through the olfactory mucosa. The olfactory path may be short and drugs might be transported through the cribriform plate within the cerebrospinal fluid draining from olfactory bulb. This may also involve the participation of trigeminal nerves.

Current drug formulations for nasal delivery use standard sprays with no specificity to the olfactory region <NUM>, relatively small molecules are used, and formulations are mainly water-based with some alcohols. For non-active ingredients in drug formulations for nasal delivery a wide variety of functionality is used: solvents, mucoadhesive, agents, absorption enhancers, viscosity modifiers, pH buffers, antioxidants, preservatives, surfactants and more.

The majority of airflow passes through the lower nares <NUM>. Therefore, sneezing would likely not expel liquids deposited in the olfactory region <NUM>. Nasal congestion may affect mainly the lower nares <NUM> while the olfactory region <NUM> stays clear.

Targeted direct-to-brain drug delivery may be achieved through saturation of the olfactory region <NUM> with an excipient/drug combination. The drug may travel via extracellular transport to the Central Nervous System, via the cribriform plate. This targeted delivery is intended to reduce both topical and system delivery, allowing for safer and more effective drug delivery.

In some embodiments the device <NUM> may be adapted by the addition of a lateral atomizer tip to achieve the current state of the art of topical drug delivery by saturating the entire mucosa, or systemic drug delivery by targeting the Upper Nares <NUM>.

The Olfactory plateau is generally located to the posterior aspect of the Radix line. This correlates to the Nasal Bridge length, which is measured from the soft tissue of the Nasion (Sellion) to the Subnasale.

<FIG> shows examples of intranasal drug delivery devices according to some embodiments with reservoir <NUM> and compliant tip <NUM>.

<FIG> shows an example release and reload mechanism <NUM> according to some embodiments. Release and reload mechanism <NUM> may be incorporated into an intranasal drug delivery devices such as, for example, device <NUM>.

The release and reload mechanism <NUM> has a reservoir <NUM> containing a drug for delivery into the nasal cavity.

The release and reload mechanism <NUM> has an insertion needle <NUM> for insertion into the reservoir <NUM>.

In some embodiments reservoir <NUM> is a bag and may be collapsible by external pressure, including ambient air pressure.

In some embodiments, reservoir <NUM> is removable and insertion needle <NUM> is inserted through a silicon stopper in the top of reservoir <NUM> for drawing the substance into the device <NUM>. The silicon stopper has re-sealing properties for air sensitive medicine. The insertion needle <NUM> can be left in the bottle from which the medicine for the device was obtained. The filling process can eliminate the need for a separate syringe. In some embodiments, this may be referred to as a lure lock.

The release and reload mechanism <NUM> has actuator <NUM> connected to release spring <NUM>.

The release and reload mechanism <NUM> has plunger <NUM>, load valves <NUM> and load chambers <NUM>.

The release and reload mechanism <NUM> has shot chamber <NUM>,fluid chamber <NUM>, release valves <NUM> and nozzle <NUM>. The nozzle <NUM> may be in fluid communication with the nib <NUM> such that fluid is ejected from nozzle <NUM> and through nib <NUM> or as described below.

In some embodiments release valves <NUM> may comprise an elongated duckbill valve in tip to reduce and valve the line/dead volume.

In some embodiments, reservoir <NUM> is held under tension by compression spring <NUM>. A constant and predetermined fluid pressure may be maintained by compression spring <NUM> pushing up from the bottom of the reservoir towards the shot chamber <NUM> and nozzle <NUM> and plunger <NUM>. This constant liquid pressure charges the load chamber <NUM> without exposing the medicine to air or metal springs typical in most nasal pumps. In some embodiments, this may avoid the use of tubing between the reservoir <NUM> and shot chamber <NUM>. This can reduce dead volume of medication or medication left in line after use. This can ensure dosing accuracy is not compromised by air entering the shot chamber <NUM> and no content remains in the shot chamber <NUM> or reservoir <NUM> after the last usable medicine was administered. The constant pressure enables dosing independent of user orientation.

According to the present invention, soft nib <NUM> is designed to discharge a laminar flow and this may include a turbulent boundary, discreet liquid slug ideally suited for maximizing dose delivery to the flat narrow section of nasal cavity leading up to the olfactory region. Delivery of laminar liquid slug assists in capillary action required for maximum medicine reaching the olfactory. In some embodiments, the laminar stream is created by tube array or hydrodynamic focusing.

In some embodiments the design of the chamber and fluid path can promote high accuracy in ejected volume.

In some embodiments device <NUM> is cocked by pushing down, or compressing, the bottle. This method of preparing the device for actuating requires very little dexterity or fine motor skills. This method of preparing the device for administrating medicine may be of particular importance to patients whose motor skills may be impaired e.g. patients with Parkinson's. The device can be oriented in any direction and the reloading of the shot chamber and the shot performance will not be affected i.e. the device is not gravity sensitive.

In some embodiments the compliant, soft nib <NUM> is extended by cocking the device. This reduces over length profile of the device for shipping, shelf space and pocketing. In the resting position the device has a less 'menacing' look.

In some embodiments cocking the device <NUM> may activate a dose counter. In some embodiments cocking may activate a separate shot counter for each dosing session.

In some embodiments cocking may activate a dose delay. In some embodiments cocking may activate a timer to remind patient when to activate between shots needed for dosing session. The delay between shots accommodates drug dosing indications including the timing of maximum drug absorption via the olfactory tight junction and the natural clearing of the mucosa cilia.

In some embodiments cocking may change the exposed color <NUM> between the upper bottle sleeve <NUM> and base <NUM>. This, along with an extended nozzle tip (which in some embodiments does not fit in the lid <NUM> while cocked) gives the patient or care giver a clear visual and/or feel the device is ready for dosing or storage. In some embodiments exposed color <NUM> is made with glow plastic for darkness which promotes ease and convenience of nighttime use and for patients sensitive to light e.g. for administering medicine that dilates pupils.

In some embodiments nozzle has an adjustable nostril stop <NUM>. This stop gives patient feedback the nozzle has arrived at the optimum nostril depth. The stop also reduces sniffing/snorting during activation.

In some embodiments, the drug may be delivered by the intranasal drug delivery device <NUM> by delivery of a liquid jet, burst or plug, rather than a spray. In some embodiments the design of the compliant, soft nib <NUM>, the nozzle <NUM>, and the valves in the reload mechanism <NUM> may be designed to optimize laminar ejection of drug.

Technology for liquid delivery works for a wide variety of liquid properties. This technology may be adapted to olfactory, systemic and topical delivery of drugs through an intranasal drug delivery device <NUM>.

In some embodiments intranasal drug delivery device <NUM> may use particular liquid properties (such as viscosity and surface tension) to ensure prolonged residence of the delivered liquid in the target area (i.e. the olfactory region) due to capillary bridging.

In some embodiments intranasal drug delivery device <NUM> may include excipients in the liquid drug for delivery with particular characteristics. For example, excipients may have thixotropicity (higher viscosity at rest which improves residence time in the olfactory region <NUM>, and lower viscosity at under shear which improves ease of metering and delivery) through additives such as cellulose. As a further example, excipients used may impact surface tension of a drug to promote wetting and capillary bridging in olfactory region. As a further example, excipients used may be pre-approved by the Federal Drug Administration for shorter development time.

In some embodiments intranasal drug delivery device <NUM> may include a measurement method or accessory to determine the ideal compliant, soft nib <NUM> size, or nozzle <NUM> type.

In some embodiments intranasal drug delivery device <NUM> may include a mechanical or electronic timer and/or lock mechanism to prevent overdosing. Intranasal drug delivery device <NUM> may incorporate use of mobile technology for identifying users and tracking use to prevent overdosing. Intranasal drug delivery device <NUM> may incorporate use of a cock-and-release mechanism to promote steady positioning during drug delivery. These additions assist with patient compliance.

In some embodiments intranasal drug delivery device <NUM> may be used in one or more of the following applications: <NUM>) drugs directly targeting the brain via the olfactory region, <NUM>) systemically acting drugs (e.g. better systemic bioavailability or less degradation than via the GI tract), <NUM>) vaccines eliciting a mucosal immune response, and <NUM>) topically-acting drugs.

In some embodiments the intranasal drug delivery device <NUM> may have one or more of the following features: <NUM>) hand held, <NUM>) useable with a single hand, <NUM>) designed for ambidextrous use, <NUM>) the priming mechanism is simple and intuitive to the user, <NUM>) there is a clear indication when the dose is primed, <NUM>) the form promotes proper positioning in the nasal cavity, <NUM>) designed to require a single user action to deliver a primed dose, <NUM>) designed to prevent the user from dispensing partial doses, and <NUM>) useable for multiple doses.

In some embodiments the intranasal drug delivery device <NUM> is intended to be filled by a pharmacist or other medical professional. In some embodiments the intranasal drug delivery device <NUM> shall contain means for preventing unintended refills of the reservoir <NUM>.

In some embodiments the intranasal drug delivery device <NUM> is designed for multiple uses. In some embodiments the intranasal drug delivery device <NUM> uses a disposable or a refillable reservoir <NUM>. In some embodiments the compliant, soft nib <NUM> is disposable.

In some embodiments intranasal drug delivery device <NUM> is designed with a floating gasket in a disposable or reusable reservoir <NUM>.

In some embodiments, the drug delivery device <NUM> may integrate with a system involving mobile technology such as, for example, face recognition and position tracking, Gyroscopic position tracking of device and correlation with facial position, use of NFC to track number of shots.

In some embodiments, the drug delivery device <NUM> may enable electrically activated drug delivery such as lontophoresis. In some embodiments, the drug delivery device <NUM> may involve applying an ionic charge to the drug molecule to enhance transport. In some embodiments, the drug delivery device <NUM> may involve an extending tip that telescopes.

In some embodiments, intranasal drug delivery device <NUM> is designed to use a foam as an excipient to assure residence time in target area yet allow air to pass.

In some embodiments intranasal drug delivery device <NUM> has barbs to lock a gasket at the end of travel to prevent misuse by refilling.

In some embodiments intranasal drug delivery device <NUM> has a piston that scores the chamber walls as it travels to the top of the reservoir with each actuation. This renders the device useless after a single use.

In some embodiments intranasal drug delivery device <NUM> is a multi-dose device with a sterile barrier to avoid contamination.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments including fluid chamber <NUM>, nozzle <NUM>, compliant, soft nib <NUM>, actuator <NUM>, exposed colour <NUM> and base <NUM>.

<FIG> shows an example intranasal drug delivery device <NUM><NUM>, <NUM> according to some embodiments: with the base <NUM> connected to the intranasal drug device <NUM>, with the base <NUM> removed and the removable reservoir <NUM> inserted into the intranasal drug delivery device <NUM>, and with the removable reservoir <NUM> partially removed from intranasal drug delivery device <NUM>. In some embodiments, a latch mechanism <NUM> retains the removable reservoir <NUM> in the device.

<FIG> shows an intranasal drug delivery device <NUM> inserted into the nasal cavity of a patient with the tip touching the olfactory region <NUM>. In some embodiments a speculum may be used as an accessory to open the nostril. In some embodiments the device <NUM> may include an accessory part to guide the tip.

The compliant, soft nib <NUM> of the device is entered into the intranasal cavity and uses the common internal nasal geometry to self-guide the compliant, soft nib <NUM> to the olfactory region. The compliant, soft nib <NUM> is held from lateral deviation via the flanking medial septum, and the lateral nasal wall.

In some embodiments when the device <NUM> is activated, an internal metering chamber ejects a repeatable and metered dose into the superior/posterior aspect of the olfactory region. According to the present invention, a laminar flow is produced, as opposed to conventional atomization or spray, to ensure that the ejected dose gets delivered to the target area, rather than spreading in the entire intranasal space. Due to the Coanda effect, the ejected excipient adheres to the medial, lateral and superior aspect of the olfactory corridor while still motive.

When the motive energy of the ejected liquid has dissipated, opposing wall capillary motion allows the excipient to coat the entire olfactory area. This is due to the combination of excipient surface tension (which is caused by cohesion within the excipient) and mucoadhesive properties between the excipient and olfactory mucosa wall.

To achieve residence time, and as a result of capillary action, the excipient will be held in the olfactory corridor due to a capillary bridge effect caused by the opposing walls of the medial, lateral and superior aspect of the olfactory corridor. Thus preventing the excipient from draining to the inferior aspect of the nasal vault. An adequately high viscosity or thixotropic property of the excipient helps prolong residence time.

In one embodiment the proposed method for targeted drug delivery using the device <NUM> is as follows: <NUM>) The compliant tip is placed to the anterior aspect of the olfactory corridor; <NUM>) The excipient is ejected out of the tip in a "reasonably" laminar jet, and towards the posterior aspect of the olfactory corridor; <NUM>) Due to the Coanda effect, jet ejection will cause the excipient to adhere to the medial, lateral and superior aspect of the olfactory corridor while still motive; <NUM>) When the motive energy of the ejected liquid has dissipated, opposing wall capillary motion allows the excipient to coat the entire olfactory area. This is due to the combination of excipient surface tension (which is caused by cohesion within the excipient) and mucoadhesive properties between the excipient and olfactory mucosa wall; <NUM>) To achieve residence time, and as a result of capillary action, the excipient will be held in the olfactory corridor due to a capillary bridge effect caused by the opposing walls of the medial, lateral and superior aspect of the olfactory corridor. Thus preventing the excipient from draining to the inferior aspect of the nasal vault. An adequately high viscosity or thixotropic property of the excipient helps prolonging residence time.

<FIG> illustrates an integrated intranasal drug-delivery platform <NUM> including an intranasal drug delivery device <NUM>, a mobile device <NUM>, an intranasal device software application <NUM>, a core application program interface <NUM>, and device generated data <NUM> that may be shared with shareholders <NUM>.

The device <NUM> can connect to a software application <NUM> installed on a mobile device <NUM> for data logging to flag or track misuse and compliance. For example, the intranasal device software application <NUM> can capture images up the nasal cavity to flag misuse, implement user biometric authentication for compliance, capture timing data of dosage for compliance, provide alerts or reminders to user and so on.

In some embodiments a software application will be available in association with the device <NUM> to create an integrated hardware and software intranasal drug-delivery platform <NUM>. This includes a database for the storage of data generated from device <NUM> that serves as a basis for extension to a permission-based personal data ecosystem platform.

In some embodiments the software application may be extended to become a platform for more broad data aggregation and permission-based sharing. A patient's personal data could be collected and exchanged with permission to/from all parties who have a role and accountability for administering (dispensed and applied) intranasal treatments. The data exchange portal would provide patient insight aimed at aligning and continuously influencing positive behavior for optimum health care delivery. The extension will facilitate sharing of different types of smartphone-based personal data to different stakeholders such as other patients, guardians, doctors, clinics, clinical trial researches, health care providers, patient medical insurers, doctor insurers, health care insurers, drug developers, pharmacies, patient peer support groups, disease/disorder researchers, disease/disorder NGO's, government regulators, law enforcement/first responders. Privacy and control of personal data are important. A user may wish to share data in certain circumstances, based on incentives or goodwill.

In some embodiments components of an integrated intranasal drug-delivery platform <NUM> may comprise an intranasal drug delivery device <NUM> that is inextricably linked with a specified medicine and an individual patient through device and patient verification; intranasal drug delivery device <NUM> that provides machine readable signals (fiducial markers) at time of scrip writing, scrip filling, patient dosing, patient possession, and device redemption (i.e. patient life cycle events); on-going data harvesting, transit, storage and retrieval capability; aggregation and anonymization of personal data into mineable and usable data sets eg. reporting, analytics, gamification, incentivizing, etc.; personal data for optimizing patient's immediate and ongoing healthcare and a permission-based sharing system.

Categories of data that an integrated intranasal drug-delivery platform <NUM> may utilize include a patient profile; stakeholder profiles to manage data that has been shared with them; non-medical passive personal data (recovery of which may be ongoing); medical / biometric personal data (recovery of which may be ongoing); event driven personal data at time of scrip writing, scrip filling, patient dosing, patient possession, and device redemption (i.e. patient lifecycle); and event driven prompting to influence immediate behavior.

For an example of an integrated intranasal drug-delivery platform <NUM> for a user that has been prescribed a drug that is dispensed with intranasal drug delivery device <NUM>, <NUM>) the user receives an alert on his/her mobile device <NUM> signaling that it's time to take a scheduled dose of drug, <NUM>) the user unlocks the mobile device <NUM> using native identity authentication (passcode, fingerprint or facial recognition) and the intranasal device software application <NUM> opens on the mobile device, <NUM>) the user touches the mobile device <NUM> to the intranasal drug delivery device <NUM> or initiates another form of recognition, <NUM>) the user uses the mobile device <NUM> for facial recognition validation, <NUM>) the intranasal device software application <NUM> prompts the user for measuring pre-actuation metrics/biometrics (relevant metrics may be determined by clinician, for example, cognition survey, HR measurement, short video capture to determine emotional state/impairment etc.), <NUM>) the user completes any inputs needed to complete pre-actuation tests, <NUM>) the intranasal device software application <NUM> determines that the intranasal drug delivery device <NUM> has been actuated (the action may be timestamped and recorded, methods for confirming actuation include Bluetooth connectivity, visual image, sound, colour change, artificial intelligence that recognizes actuation), <NUM>) the intranasal device software application <NUM> prompts the user for measurements of post-actuation biometrics (relevant metrics may be determined by clinicians); <NUM>) the user is taken back to dashboard as part of an interface controlled by software application <NUM> where he/she can track different metrics and manage permissions (who can see what data).

<FIG> shows an example single use intranasal drug delivery device <NUM>, pump <NUM> incorporating a reservoir, a pump locking mechanism <NUM>, and compliant, soft nib <NUM>, with a nib locking mechanism <NUM>, shot chamber <NUM> and spray tip <NUM>. In some embodiments the pump <NUM> would be a spring actuated piston and the pump locking mechanism <NUM> would lock with the nib locking mechanism <NUM>.

In some embodiments the device can include an olfactory marker that will be included with the excipient/drug that will provide biofeedback to the user. This may take the form of olfactory active marker that can signal to the user that the drug/excipient has been delivered to the olfactory region. This may include, but not be limited to markers which provide feedback of missed, un-deployed, deployed or over deployed drug/excipient. The marker can be included in the drug/excipient formulation or in some embodiments be added during the ejection process. In some embodiments, the marker may be included without the active drug agent to provide feedback to the user that an application and dosage (without the drug agent) was successful soliciting a psychological response.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments. The device <NUM> comprises an outer chassis <NUM> with a dispensing opening at a first end and an actuating opening at a second end. A dispensing tip is coupled to the dispensing opening, and an actuator <NUM> is coupled to the actuating opening. As described below, fluid can be delivered to a nasal volume through the dispensing tip by pressing on the actuator <NUM>.

In some embodiments, the device <NUM> is configured to receive a carpule <NUM> (which comprises a diaphragm <NUM>, tube <NUM>, shot chamber <NUM>, and plunger <NUM> as described below) pre-filled with a fluid, such as for example a pharmaceutical fluid. In the <FIG> example, the device <NUM> comprises an enclosure <NUM> slidably received within the outer chassis <NUM> and shaped to accept a carpule <NUM>.

The carpule <NUM> comprises a tube <NUM> with an interior shot chamber <NUM> that contains a fluid. In some embodiments, shot chamber <NUM> may carry medication, such as ketamine or other pharmaceuticals, for delivery to a patient's nasal cavity or olfactory region. The shot chamber <NUM> has a plunger <NUM> on one end, and a diaphragm <NUM> on the opposite end from the plunger <NUM>. The device <NUM> is configured such that when a user engages the actuator <NUM>, the fluid in the shot chamber <NUM> is delivered through the dispensing tip with predetermined flow characteristics. According to the present invention, illustrated in <FIG>, the dispensing tip comprises a flexible cannula or nib <NUM> configured to deliver a laminar liquid slug, as described above.

In some embodiments, plunger <NUM> may be engaged by a push rod <NUM>. In the <FIG> example, the push rod <NUM> is located at the bottom of the enclosure <NUM>, and a spring <NUM> is compressed between the push rod <NUM> and a push button <NUM>. A locking mechanism <NUM> holds the push rod <NUM> and prevents it from engaging with plunger <NUM> until the push button <NUM> is pressed. In the illustrated example, the locking mechanism <NUM> comprise a pair of pivotable tabs with inner ends engaging the push rod and outer ends extending past the outer edges of the enclosure <NUM> such that when the enclosure <NUM> is pushed into the chassis <NUM> by pressing on the push button <NUM> the tabs pivot to release the push rod <NUM>. In other embodiments, the locking mechanism may comprise one or more tabs of a lock material which is breakable by pressing on the push button <NUM>.

The diaphragm <NUM> is puncturable by the needle <NUM>. Needle <NUM> connects to channel <NUM> in flexible nib <NUM>, which may be inserted into the nasal cavity for fluid delivery as described above. When engaged, the fluid in shot chamber <NUM> is forced through needle <NUM> and channel <NUM> into the nasal cavity. Arms <NUM> may assist the user in gripping device <NUM> and engaging push button <NUM>.

In some embodiments, to assemble device <NUM>, carpule <NUM> may be inserted into the carpule enclosure <NUM>. The carpule enclosure <NUM> may then be inserted into outer chassis <NUM>. In the illustrated example, the chassis <NUM> comprises a resilient lip <NUM> and the actuator opening deforms slightly to receive the carpule enclosure <NUM> and carpule <NUM>, then holds them within the chassis <NUM>. In other embodiments, seals may be added to assist in detection of tampering.

Use of a carpule may be advantageous in certain situations because it is a commonly manufactured vessel for medication and may be made of a material that is nonreactive with medication, such as glass.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments, wherein carpule <NUM> is inserted in carpule enclosure <NUM> and the carpule enclosure <NUM> is inserted in outer chassis <NUM>, but the actuator <NUM> has not been engaged by the user and locking mechanism <NUM> holds push rod <NUM> such that plunger <NUM> is not engaged and fluid in shot chamber <NUM> is not under pressure. Arms <NUM> may be folded outward or inward against outer chassis <NUM>. The device <NUM> may be stored without the fluid in shot chamber <NUM> being under pressure. Flexible nib <NUM> may be placed in the nasal cavity of the patient prior to the actuator <NUM> being engaged by the user.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments, wherein the user has engaged the push button <NUM>, for example, by pushing it with their thumb. The user may hold the device <NUM> in their hand using arms <NUM> in a folded out orientation. When user pushes the push button <NUM>, the locking mechanism <NUM> releases push rod <NUM>. In some embodiments, the locking mechanism may comprise one or more tabs that break off to release push rod <NUM>, making the device <NUM> useable only once. In other embodiments, the locking mechanism may comprise one or more tabs that fold or cantilever out of the way to release push rod <NUM>. When the locking mechanism <NUM> is engaged it prevents the push rod <NUM> from exerting pressure on the plunger <NUM>.

When the push rod <NUM> presses against the plunger <NUM> it puts the fluid in shot chamber <NUM> under pressure, and will move the carpule <NUM> toward the needle. In some embodiments, a spring <NUM> may be included to such that the push rod <NUM> exerts even pressure on plunger <NUM>, and once the locking mechanism <NUM> is released the spring <NUM> will cause carpule <NUM> to move further into outer chassis <NUM> toward needle <NUM> until needle <NUM> punctures diaphragm <NUM>. In some embodiments a user continues to push on the push button <NUM> to move the carpule <NUM> into outer chassis <NUM> until the needle <NUM> punctures diaphragm <NUM>.

In some embodiments, actuator <NUM> may be a push button located at the bottom of device <NUM>, in other embodiments, actuator <NUM> may be located on the side of outer chassis <NUM>.

In some embodiments, device <NUM> may be designed for one-time use, with a locking mechanism <NUM> comprising tabs that break off, or other sacrificial clips or structures such that carpule enclosure <NUM> may not be removed from outer chassis <NUM> to replace the spent carpule <NUM> with a new carpule <NUM> without the device <NUM> being damaged.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments, wherein the user has pushed the actuator <NUM> such that it causes the needle <NUM> to puncture diaphragm <NUM> so that the tip of needle <NUM> is in contact with the fluid in shot chamber <NUM>. The fluid in shot chamber <NUM> is under pressure from the plunger <NUM> and may enter needle <NUM> and flow through channel <NUM> in nib <NUM>. Fluid may flow through channel <NUM> to be deposited in the nasal cavity or olfactory region of a patient.

<FIG> shows an example intranasal drug delivery device <NUM> according to some embodiments, wherein the user has pushed the actuator <NUM> such that push rod <NUM> has pushed plunger <NUM> to reach diaphragm <NUM>, ending the ejection of fluid.

<FIG> shows an external view of an example intranasal drug delivery device <NUM> according to some embodiments, wherein arms <NUM> are hinged with hinge <NUM> and may be folded against outer chassis <NUM> for storage, packing and transport. Hinge <NUM> may be a living hinge comprised of thin material, for example.

<FIG> shows an external view of an example intranasal drug delivery device <NUM> according to some embodiments, wherein arms <NUM> are folded outward from the outer chassis <NUM>, providing a grip for the user when using the device <NUM>. In the folded out position arms <NUM> may provide a grip for a user wearing gloves or a user with dexterity challenges.

<FIG> shows an unclaimed example intranasal drug delivery device <NUM> according to some embodiments, wherein the dispensing tip comprises an atomizer <NUM> designed to deliver a spray of fluid into the nasal cavity rather than a laminar liquid slug.

<FIG> show an example intranasal drug delivery device <NUM> according to some embodiments, wherein a two stage triggering mechanism is executed with a single button push.

When actuator <NUM> is first pushed by a user, the carpule <NUM> is pressed into a needle <NUM>. The needle <NUM> pierces the diaphragm <NUM> (i.e. the carpule septum) and opens a fluid path through the channel <NUM> (cannula) as shown in <FIG>. Actuator <NUM> is connected directly to plunger <NUM>. When the actuator <NUM> is pressed a second time by a user, spring <NUM> releases and depresses the plunger <NUM>, ejecting fluid through the channel <NUM> as shown in <FIG>.

Spring <NUM> may be released by breaking a shear pin <NUM> into pieces <NUM> and <NUM>, as shown in <FIG>. In other embodiments the spring <NUM> may be released when injection molded breakoff points or wings snap off of the plunger <NUM>. In other embodiments the spring <NUM> may be released by a ball detent mechanism, molded snap fit component or other mechanism that is activated by reaching a pre-set force. In still other embodiments the spring <NUM> may be released by the press force separating a magnet in the plunger from a magnet in the system body.

The travel of plunger <NUM> is limited by a stop mechanism <NUM> to set a total dose. Stop mechanism may comprise actuator projections <NUM> that engage the base of the carpule <NUM>.

<FIG> show an example intranasal drug delivery device 1900A according to some embodiments, wherein a two stage triggering mechanism is executed with a single pushing motion. In this embodiment, the actuator 1902A is connected to spring 1912A, which is connected to plunger 1914A. After actuator 1902A is pushed by a user, the carpule 1904A is pressed into a needle 1906A and the needle 1906A pierces the diaphragm 1908A and opens a fluid path through the channel 1910A (cannula) as shown in <FIG>, a further press on the actuator 1902A builds up spring force in the user's hand (or other method used to press the button). When sufficient spring force is achieved, the actuator 1902A is released. The actuator 1902A may be released by several different methods, as described above. The spring force built up behind the actuator 1902A then rapidly compresses the spring 1912A between the actuator 1902A and the plunger 1914A. The spring 1912A then dispenses the fluid from the channel 1910A.

In some embodiments, the device comprises a dampening mechanism, examples of which are described further below with reference to <FIG>. Elements such as the dispensing tip, the needle that pierces the diaphragm, and an outer body are not shown in all views, but may be included in some embodiments. In each of these example embodiments, the device <NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM>/<NUM> is configured to eject a jet of fluid through a channel with a controlled velocity profile. This assists in limiting shear on the delivered drug, some of which may be damaged by shear. For example, in some embodiments the device is configured to eject a jet of fluid starting at a high initial velocity but dropping linearly to a near zero jet velocity at the end of jet dispensing.

<FIG> shows an example device <NUM> according to some embodiments, wherein a plunger <NUM> is pushed by a spring <NUM>. In the <FIG> embodiment, the velocity of the plunger <NUM> is controlled by an eddy current brake connected to the traveling end of the spring <NUM>. In the <FIG> embodiment, the dampening mechanism comprises a magnet <NUM> connected to the plunger <NUM> moves through a conductive jacket <NUM>, generating eddy currents and limiting the maximum plunger speed. In another embodiment the velocity of the plunger <NUM> may be controlled by having magnet <NUM> spun by a helix on a shaft connected to the traveling end of the spring (not shown).

<FIG> shows an example device <NUM> according to some embodiments, wherein the velocity of the plunger <NUM> travel is controlled by a dampening mechanism inherently formed by the construction of the device <NUM> and the materials chosen. For example, in some embodiments part tolerances and material variations are controlled to provide a plunger <NUM> friction and spring <NUM> value configured to ensure desired jet velocity profile.

<FIG> shows an example device <NUM> according to some embodiments, wherein the velocity of the plunger <NUM> is controlled by a dampening mechanism comprising a viscous dampener <NUM> connected to the traveling end of the spring <NUM>. The dampener <NUM> is filled with air or with viscous liquid (e.g. oil). The dampener <NUM> controls the velocity of the traveling end of the spring <NUM>. Maximum velocity is limited by the dampener <NUM>, and as the spring <NUM> extends, it's driving force decreases. This provides an initially high velocity followed by a decrease in velocity over the total dispensed volume.

<FIG> shows an example device <NUM> according to some embodiments, wherein the velocity of the plunger <NUM> is controlled by a dampening mechanism comprising a sealed chamber <NUM> attached to the back of the device <NUM> connected to a spring <NUM>, which is connected to the plunger <NUM>. Air must be drawn into the chamber <NUM> to allow the plunger <NUM> to advance, but air flow into the chamber <NUM> is limited by ether <NUM>) a flow control valve (not shown) or <NUM>) a simple flow restriction <NUM> (e.g. narrow channel, orifice plate).

<FIG> shows an example device <NUM> according to some embodiments, wherein the dampening mechanism comprises a spring <NUM> used to compress a body of air (e.g. pushing on a bellows, pushing on a diaphragm, pushing a piston) into a sealed chamber <NUM>. The compressed air flow through a flow restriction <NUM> that controls air flow rate to the device <NUM>. The outside of the device <NUM> body seals to the sealed chamber <NUM> (e.g. O-ring seal). The air then pushes on the back side <NUM> of the piston <NUM>, pushing the drug out of the channel <NUM>. Because the flow rate of air is controlled by the flow restriction <NUM>, the rate of travel for the piston <NUM> is controlled. The flow restriction <NUM> may be simple, like an orifice plate, narrow tube, or narrow drilled hole, but it may also be a pneumatic device like a pressure relief valve, or flow control valve.

<FIG> show an example device <NUM> according to some embodiments, wherein control over the velocity of the plunger <NUM> is be achieved by a dampening mechanism comprising a container <NUM> of compressed gas (e.g. CO2 canister, sealed canister of air, N2, etc.). The container <NUM> of compressed gas is connected to the flow restriction <NUM> by piercing a membrane <NUM> or septum or by connecting with a valve. A leak point may be added to the chamber to cause pressure applied to the device <NUM> to dissipate over time. This provides a decreasing velocity profile for the fluid jet. The compressed gas container may be connected to the device <NUM> chamber by piercing a membrane on the canister, by a valve, or by a similar mechanism.

<FIG> show an example device <NUM> according to some embodiments, wherein the dampening mechanism comprises a piston <NUM>, sealed chamber <NUM>, pin and ball valve <NUM>. In this embodiment, the piston <NUM> is moved and compressed gas in sealed chamber <NUM> is provided instantaneously using a mechanically operated valve such as pin and ball valve <NUM>. When the piston <NUM> reaches the top of the chamber <NUM>, a pin <NUM> is pushed by the piston <NUM>, opening a ball valve <NUM> to release pressure into the shot chamber <NUM>.

<FIG> shows an example device <NUM> according to some embodiments, wherein a plunger <NUM> is pushed by an electric motor <NUM> (e.g. stepper motor, DC motor, brushless motor, etc.) which provides the function of both actuating force and a dampening mechanism. Circuitry onboard the electric motor <NUM> controls the plunger <NUM> velocity to set the desired ejected fluid velocity profile. Control of the electric motor <NUM> may be open loop or closed loop. Motor <NUM> may be a liner motor, or a rotary motor combined with gearing, a linkage, cam, lead screw, or other mechanical element to drive the plunger <NUM>.

<FIG> show an example device <NUM> according to some embodiments, wherein controlled jet velocity is provided by a dampening mechanism comprising an elastomeric chamber <NUM>. This occurs in two steps. First, the plunger <NUM> is depressed to fill the elastomeric chamber <NUM>, as shown in <FIG>. Second the fluid path to the channel <NUM> is opened, now spring force stored in the stretched elastomeric chamber <NUM> forces the fluid out of the channel <NUM> as shown in <FIG>.

The flow resistance of the fluid path out of the elastomeric chamber <NUM> is matched to the stiffness of the elastomeric chamber <NUM> to provide a controlled jet velocity profile. As the elastomeric chamber <NUM> relaxes, the pressure on the fluid decreases, so this provides an initial high velocity followed by a decrease in jet velocity.

<FIG> show an example device <NUM> according to some embodiments, wherein a carpule <NUM> is depressed to fill the elastomeric chamber <NUM> and the fluid path to channel <NUM> is opened with a single motion. In this embodiment, a needle <NUM> is partially embedded in a septum <NUM> to seal the end of the needle <NUM>, as shown in <FIG>. First, as the plunger <NUM> moves, the diaphragm <NUM> is pierced. As the plunger <NUM> continues to move as shown in <FIG>, the elastomeric chamber <NUM> is loaded with fluid. The spring <NUM> prevents travel of the carpule <NUM> until the plunger <NUM> is sufficiently depressed. Third, the plunger <NUM> travel ends, the spring <NUM> is compressed, and the septum <NUM> is pierced by needle <NUM> as shown in <FIG>. Fourth, the elastomeric chamber <NUM> forces fluid out through the channel <NUM>. As the elastic elastomeric chamber <NUM>, pressure drops, providing a decreasing velocity profile. Chamber geometry can be varied to make a linear or non-linear decreasing velocity profile.

<FIG> shows an example device <NUM> according to some embodiments, wherein a large spring <NUM> with a limited initial travel is used to break static friction in the piston <NUM> and a second spring <NUM> provides the force to fully dispense the drug. Large spring <NUM> is a higher force spring than second spring <NUM>. The flow path out of the channel <NUM> is long enough that the high velocity travel from the large spring <NUM> does not cause fluid to leave the channel <NUM>.

<FIG> shows an example device <NUM> according to some embodiments, wherein the flow rate of the jet is controlled by a flow restriction device <NUM> between a carpule <NUM> and a channel <NUM>. The flow restriction device <NUM> can be long and gradual to keep a laminar flow profile. This will prevent excessive shear on the delivered drug (e.g. protecting the viability of vaccines). The flow restriction device <NUM> could also be more compact but producing a turbulent flow. This would make a more compact device suitable for delivering robust therapeutic agents. The flow restriction device <NUM> could also be replaced by an active element like a constant velocity flow control valve, a pressure relief valve, or a pressure control valve.

<FIG> show an example device <NUM> according to some embodiments, wherein the plunger <NUM> is driven by a spring <NUM>, but piston velocity is controlled by bellows <NUM> filled with air. As the piston <NUM> travels up, the bellows <NUM> are compressed, and air is forced through a flow restriction <NUM> (e.g. simple orifice plate, small drilled hole, pressure control valve, flow rate control valve). The rate that the bellows <NUM> can deform is controlled by the rate of air flow through the flow restriction <NUM>. This could be accomplished by an arrangement where air is contained in a diaphragm <NUM>, rolling diaphragm or a piston as shown in <FIG>. It may also be accomplished in the same configuration shown in <FIG> but with a diaphragm, rolling diaphragm, or piston.

Air may vent externally to the device, or it may vent into a secondary chamber to avoid the need for an external vent.

A prototype device including a cannula and dampening mechanism has been tested to demonstrate targeted delivery of the fluid bolus. The testing comprised inserting the cannula into the upper nares of a patient and ejecting a laminar flow of fluid through the cannula. In the testing, technicium <NUM> was used as a tracer fluid. A scan of the patient performed following the injection of the laminar flow of fluid show that the fluid is deposited at the olfactory region of the patient <NUM>, as shown in <FIG>. The presence of the technicium <NUM> appears as a light region on the scan shown in <FIG>.

The inventive subject matter is defined by the appended claims.

The embodiments of the devices, systems and methods described herein may be implemented in a combination of both hardware and software. These embodiments may be implemented on programmable computers, each computer including at least one processor, a data storage system (including volatile memory or non-volatile memory or other data storage elements or a combination thereof), and at least one communication interface.

Program code is applied to input data to perform the functions described herein and to generate output information. The output information is applied to one or more output devices. In some embodiments, the communication interface may be a network communication interface. In embodiments in which elements may be combined, the communication interface may be a software communication interface, such as those for inter-process communication. In still other embodiments, there may be a combination of communication interfaces implemented as hardware, software, and combination thereof.

Throughout the foregoing discussion, numerous references will be made regarding servers, services, interfaces, portals, platforms, or other systems formed from computing devices. It should be appreciated that the use of such terms is deemed to represent one or more computing devices having at least one processor configured to execute software instructions stored on a computer readable tangible, non-transitory medium. For example, a server can include one or more computers operating as a web server, database server, or other type of computer server in a manner to fulfill described roles, responsibilities, or functions.

Although the embodiments have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein.

Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification.

Claim 1:
An intranasal fluid delivery device (<NUM>) comprising:
(a) a dispensing tip (<NUM>) having a compliant or flexible soft nib (<NUM>), the dispensing tip being connected to a hollow needle (<NUM>);
(b) a shot chamber (<NUM>) configured to carry a fluid, the shot chamber having a diaphragm (<NUM>) at a first end and a plunger (<NUM>) at a second end; and
(c) an actuator (<NUM>) connected to a push rod (<NUM>) moveable toward the second end of the shot chamber and having a locking mechanism (<NUM>), wherein pushing the actuator releases the locking mechanism, allowing the push rod to push against the plunger, exerting pressure on the fluid and forcing the needle through the diaphragm into the shot chamber such that the fluid flows out of the needle into the dispensing tip;
wherein the nib (<NUM>) defines a channel (<NUM>) therein for dispensing the fluid therefrom as a laminar flow, wherein the nib is biased to follow a user's septum such that the dispensing tip complies with the internal nasal geometry to position an end of the dispensing tip proximate to the olfactory region, such that the dispensing tip is capable of delivering the fluid to the olfactory region in the user's nasal cavity.