Patent Description:
There are many different ways in which a drug can be administered to a user. Depending on the drug, intranasal drug delivery can be one of the most effective ways to achieve desired clinical benefits in a timely manner and in a manner that is convenient and comfortable for a patient.

Intranasal drug administration is a non-invasive route for drug delivery. Since the nasal mucosa offers numerous benefits as a target tissue for drug delivery, a wide variety of drugs may be administered by intranasal systemic action. Moreover, intranasal drug delivery can avoid the risks and discomfort associated with other routes of drug delivery, such as intravenous drug delivery, and can allow for easy self-administration.

Generally, to maximize the efficacy of the drug through intranasal administration, the majority volume of the aerosolized dose of the drug needs to reach the correct region of the nasal cavity. As such, additional measures may need to be taken for effective intranasal drug delivery. For example, the user may need to have a clear nostril, tilt their head back at approximately <NUM>°, close the opposite nostril, and then sniff gently while the dose of drug is administered. In order to coordinate these measures, and given that nasal administration is intimate, self-administration by the user may be desired. Further, due to the nasal cycle (alternating physiological partial congestion of the nasal turbinate to facilitate nasal function) or pathological congestion, one nostril is likely to provide a more effective drug delivery route than the other nostril at any given time. As such, it is desired that an equal dose of the drug be delivered to each nostril of the user to inhibit under-dosing of the drug.

Dual-dose intranasal drug delivery devices are available that are designed for self-administration of two distinct aerosolized sprays, one for each nostril, that together constitute one dose of drug. Such drug delivery devices require a series of operational steps that the user needs to properly carry out to effect optimal drug delivery through self-administration. After the drug is delivered, the device may be disposed of as a used device having no drug remaining in the device or having a residual amount of the drug remaining in the device that cannot be further delivered from the device. Disposing the device after use may have adverse environmental impacts by generating waste that cannot be recycled, that is accidentally not recycled, or that cannot be efficiently recycled from the particular geographic region of the device's use. Some nasal drug delivery devices are designed for one-time use to deliver one dose of drug, such as for prescription drugs where the amount of drug delivered to the patient is important and is typically prescribed at a certain amount per dose. Such one-time use devices may therefore have exacerbated adverse environmental impacts since they are not reused before disposal.

Additionally, one-time use nasal drug delivery devices prevent patients from becoming familiar and comfortable with using the same device for multiple drug deliveries. Even if each sequentially used nasal drug delivery device is the same as one another, at least some patients may not recognize each device's similarity and/or may feel reluctance and/or nervousness at using a device they have never used before.

Accordingly, there remains a need for improved nasal drug delivery devices.

In <CIT>, there is described an apparatus and method for the self-administration of a plurality of doses of an intranasal liquid pharmaceutical composition, including opioid analgesics, that includes a drug delivery device containing a plurality of sealed vials, each vial containing a predetermined volume of the pharmaceutical composition, a pump assembly for conveying the liquid pharmaceutical composition from the interior of the vial and discharging it as a nasal spray in response to manual activation by the patient, and programmable means for sequentially advancing a vial to the ready position after passage of a prescribed time interval following the last activation of the delivery device.

In <CIT>, there is described a method of treatment and a nasal delivery device for dosages containing dissolved gaseous carbon dioxide in saline fluid for treating head ailments.

In <CIT>, there is described a dispenser device for fluid or powder, including an air expeller and a reservoir.

In <CIT>, there is described a dispenser, especially a disposable atomizer, with a dispenser unit.

In general, reloadable drug vials for multi-dose delivery, drug products utilizing the same, and methods of using reloadable drug vials for multi-dose delivery are provided.

The present invention is described by way of reference to the accompanying figures which are as follows:.

Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the devices, systems, and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. A person skilled in the art will understand that the devices, systems, and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present invention.

A person skilled in the art will appreciate that a dimension may not be a precise value but nevertheless be considered to be at about that value due to any number of factors such as manufacturing tolerances and sensitivity of measurement equipment. Sizes and shapes of the systems and devices, and the components thereof, can depend at least on the size and shape of components with which the systems and devices will be used.

Various exemplary reloadable drug vials for multi-dose delivery, drug products utilizing the same, and methods of using reloadable drug vials for multi-dose delivery are provided. In general, a nasal drug delivery device is configured to releasably couple to a first drug holder that contains a drug therein to be dispensed by the drug delivery device. After the drug is delivered from the drug delivery device, the first drug holder is configured to be removed from the drug delivery device and replaced with a second drug holder containing a drug therein to be dispensed by the drug delivery device. The same drug delivery device is therefore configured to deliver multiple doses. After the drug is delivered from the drug delivery device, the drug delivery device and the second drug holder releasably coupled thereto can be disposed of as waste. Alternatively, after the drug is delivered from the drug delivery device, the second drug holder can be removed from the drug delivery device and replaced with a third drug holder containing a drug therein to be dispensed by the drug delivery device and so on with one or more additional drug holders sequentially being coupled to and used in delivering a drug from the drug delivery device.

Replacing a drug holder after drug delivery allows a remainder of the drug delivery device to be re-used, thereby generating less waste than drug delivery devices that are disposed of after use with the drug holder used with the drug delivery device. Replacing the drug holder after drug delivery allows for one drug delivery device to be purchased that can be used for a plurality of dose deliveries instead of requiring multiple drug delivery devices with pre-loaded drug holders to be purchased to deliver that same number of doses, thereby reducing health care expenses since fewer drug delivery devices need to be purchased. Replacing the drug holder after drug delivery allows for the same drug delivery device to be repeatedly used by the same user for a plurality of dose deliveries, which may allow for the user to develop familiarity and confidence in the device over time and/or may reduce user reluctance and/or nervousness in using the device since (after the first use) they are not using a device they have never used before.

In an exemplary embodiment, the drugs in each of the drug holders configured to be releasably coupled to the drug delivery device are the same such that the drug delivery device is usable to deliver subsequent doses of the same drug to a user of the drug delivery device. The user may therefore be able to use the same drug delivery device repeatedly in fulfilling a drug prescription. In other embodiments, the drugs in each of the drug holders configured to be releasably coupled to the drug delivery device are not all the same such that the drug delivery device is usable to deliver doses of different drugs to a user of the drug delivery device. The user may therefore be able to use the same drug delivery device repeatedly in fulfilling two or more drug prescriptions. In embodiments in which the drugs in each of the drug holders are not all the same, at least one of the drug holders contains a first drug therein and at least one of the drug holders contains a second drug that is different than the first drug. In embodiments in which at least three drug holders are provided for releasable coupling to the drug delivery device, the number of different drugs contained in the various drug holders can be more than two.

The drug to be delivered using a drug delivery device as described herein can be any of a variety of drugs. Examples of drugs that can be delivered using a drug delivery device as described herein include antibodies (such as monoclonal antibodies), hormones, antitoxins, substances for the control of pain, substances for the control of thrombosis, substances for the control of infection, peptides, proteins, human insulin or a human insulin analogue or derivative, polysaccharide, DNA, RNA, enzymes, oligonucleotides, antiallergics, antihistamines, anti-inflammatories, corticosteroids, disease modifying anti-rheumatic drugs, erythropoietin, and vaccines. Examples of drugs that can be delivered using a drug delivery device as described herein include ketamine (e.g., Ketalar®), esketamine (e.g., Spravato®, Ketanest°, and Ketanest-S°), naloxone (e.g., Narcan°), and sumatriptan (e.g., Imitrex®).

In an exemplary embodiment, the drug holder configured to be releasably coupled to the drug delivery device is a vial. An exemplary vial is formed of one or more materials, e.g., glass, polymer(s), etc. In some embodiments, a vial can be formed of glass. In other embodiments, a vial can be formed of one or more polymers. In yet other embodiments, different portions of a vial can be formed of different materials.

<FIG> illustrates one exemplary embodiment of a drug holder in the form of a vial <NUM> configured to contain a drug therein. The vial <NUM> includes a base or distal portion <NUM> and a head or proximal portion <NUM>. As shown, the vial <NUM> also includes an inwardly tapering neck portion <NUM> that extends between the base portion <NUM> and the head portion <NUM>. The inwardly tapering neck portion <NUM> allows the head portion <NUM> to have a maximum outer diameter 104D that is less than a maximum outer diameter 102D of the base portion <NUM>. The head portion <NUM> having a smaller maximum outer diameter 104D than the base portion's maximum outer diameter 102D may ease coupling of the vial <NUM> to a drug delivery device in embodiments in which a user holds the base portion <NUM> and inserts the vial <NUM> proximally into the drug delivery device by providing a larger area of the vial <NUM> for the user to hold (e.g., the base portion <NUM>) and a smaller area of the vial <NUM> to lead the insertion of the vial <NUM> into the drug delivery device (e.g., the head portion <NUM>). In other embodiments, the taper between the base and head portions <NUM>, <NUM> can be omitted, and the base and head portions <NUM>, <NUM> can have a same maximum outer diameter 102D, 104D as one another.

The base portion <NUM> defines a hollow interior <NUM> within the base portion <NUM> that is configured to contain the drug therein. In an exemplary embodiment, an amount of the drug in the vial <NUM> is such that the drug can be contained entirely within the hollow interior <NUM> of the base portion <NUM>, but the amount of the drug can be such that drug entirely fills the hollow interior <NUM> of the base portion <NUM> and also fills at least some part of the neck portion <NUM> and optionally also at least some part of the head portion <NUM>. While the base portion <NUM> can have a variety of configurations, in this illustrated embodiment, the base portion <NUM> has a substantially cylindrical shape. In other embodiments, the base portion <NUM> can have any other suitable shapes, e.g., a substantially rectangular shape, etc. A person skilled in the art will appreciate that a shape may not be a precise shape (e.g., a precise cylinder or a precise rectangle) but nevertheless be considered to be substantially that shape due to any number of factors, such as manufacturing tolerances and sensitivity of measurement equipment.

The vial <NUM> includes a seal member <NUM> in the form of a septum at a proximal end thereof in the head portion <NUM>. The seal member <NUM> is configured to provide a fluid tight seal such that the drug is contained in the vial <NUM> until the seal provided by the seal member <NUM> is broken. The seal provided by the seal member <NUM> can be broken in a variety of ways, such as by being pierced by a needle of the drug delivery device to which the vial <NUM> is releasably coupled. The seal member <NUM> can have a variety of configurations, as will be appreciated by a person skilled in the art, such as by being a pierceable polymer septum or a foil layer. The seal member <NUM> can be protected from accidental puncturing or piercing before intended use with a removable protective member or stopper, such as a TE seal, etc. In some embodiments, the seal member <NUM> can be omitted and instead a removable protective member or stopper can be provided that is removed just prior to use of the vial <NUM>.

An exemplary vial can include a variety of features to facilitate sealing and storing a drug therein, as described herein and illustrated in the drawings. However, a person skilled in the art will appreciate that the vials can include only some of these features and/or can include a variety of other features known in the art. The vials described herein are merely intended to represent certain exemplary embodiments.

A drug delivery device configured to releasably couple to a vial can have a variety of configurations. In general, the drug delivery device is configured to deliver a drug to a patient, where the drug is provided in a defined dosage form within the drug delivery device.

<FIG> illustrates one embodiment of a drug delivery system <NUM> including a drug delivery device <NUM> configured to releasably couple to a vial <NUM>, such as the vial <NUM> of <FIG>. As will be appreciated by a person skilled in the art, the drug delivery device <NUM> and the vial <NUM> can each include different features in different embodiments depending upon various requirements, such as the type of drug, typical dosage(s) of the drug, safety requirements in various jurisdictions, whether the device is powered, etc..

<FIG> illustrates an exemplary embodiment of the drug delivery device <NUM> of <FIG> illustrates a drug delivery device <NUM> that includes a coupling mechanism <NUM> configured to releasably couple to a vial, such as the vial of <FIG>. The coupling mechanism <NUM> can have a variety of configurations, as discussed further below.

The drug delivery device <NUM> also includes a dispensing mechanism <NUM> that is configured to be operatively coupled to the vial releasably coupled to the coupling mechanism <NUM> and that is configured to release a drug from the drug delivery device <NUM>, e.g., from the vial releasably coupled to the coupling mechanism <NUM>, so that the drug can be administered to a patient. The dispensing mechanism <NUM> can have a variety of configurations. For example, the dispensing mechanism <NUM> can include a piston and/or a needle configured to pierce through or puncture a seal member of the vial releasably coupled to the drug delivery device <NUM>.

The drug delivery device <NUM> also includes an actuator <NUM> configured to be actuated by a user to cause the dispensing mechanism <NUM> to begin delivering a dose of the drug through an opening or nozzle <NUM> in the drug delivery device <NUM>. In an exemplary embodiment, the drug delivery device <NUM> is configured to be self-administered such that the user who actuates the actuator <NUM> is the patient receiving the drug from the drug delivery device <NUM>.

The opening <NUM> through which the drug exits the drug delivery device <NUM> is formed in a dispensing head <NUM> of the drug delivery device <NUM> in a tip <NUM> of the dispensing head <NUM>. The tip <NUM> is configured to be inserted into a nostril of a patient. In an exemplary embodiment, the tip <NUM> is configured to be inserted into a first nostril of the patient during a first stage of operation of the drug delivery device <NUM> and into a second nostril of the patient during a second stage of operation of the drug delivery device <NUM>. The first and second stages of operation involve two separate actuations of the actuator <NUM>, a first actuation corresponding to a first dose of the drug being delivered and a second actuation corresponding to a second dose of the drug being delivered. The dispensing head <NUM> includes a depth guide <NUM> configured to contact skin of the patient, e.g., between the patient's first and second nostrils, such that a longitudinal axis of the dispensing head <NUM> is substantially aligned with a longitudinal axis of the nostril in which the tip <NUM> is inserted. A person skilled in the art will appreciate that the longitudinal axes may not be precisely aligned but nevertheless be considered to be substantially aligned due to any number of factors, such as manufacturing tolerances and sensitivity of measurement equipment.

In an exemplary embodiment, the dispensing head <NUM> has a tapered shape in which the dispensing head <NUM> has a smaller diameter at its distal end than at its proximal end where the opening <NUM> is located. The opening <NUM> having a relatively small diameter facilitates spray of the drug out of the opening <NUM>, as will be appreciated by a person skilled in the art. A spray chamber through which the drug is configured to pass before exiting the opening <NUM> is located within a proximal portion of the tapered dispensing head <NUM>, distal to the opening <NUM>. When the drug passes through the spray chamber at speed, the spray chamber facilitates production of a fine mist that exits through the opening <NUM> with a consistent spray pattern.

The drug delivery device <NUM> also includes a device indicator <NUM> configured to present information to a user about a status of the drug delivery device <NUM> and/or the drug contained in the vial releasably coupled to the drug delivery device <NUM>. The device indicator <NUM> can be a visual indicator, such as a display screen, one or more lights, one or more colored and/or numbered markings, etc. Alternatively or in addition, the device indicator <NUM> can be an audio indicator configured to provide sound.

The drug delivery device <NUM> also includes a sensor <NUM> configured to sense information relating to the drug delivery device <NUM> and/or the drug contained in the vial releasably coupled to the drug delivery device <NUM>. Examples of information that the sensor <NUM> can sense include environmental conditions (e.g., temperature, humidity, geographic location, time, etc.) and drug holder status (e.g., whether or not a vial is releasably coupled to the coupling mechanism <NUM>). The drug delivery device <NUM> can also include a communications interface <NUM> configured to communicate externally data which has been gathered by the sensor <NUM> about the drug delivery device <NUM> and/or the drug contained in the vial releasably coupled to the drug delivery device <NUM>, which may facilitate analysis regarding the patient's treatment, patient compliance, use of the drug delivery device <NUM>, etc..

In embodiments in which the drug delivery device <NUM> includes one or more electrical components, e.g., the device indicator <NUM> (which in some embodiments can be powered while in other embodiments not be powered), the sensor <NUM>, the communications interface <NUM>, a processor <NUM>, a memory <NUM>, etc., the drug delivery device <NUM> includes a power supply <NUM> configured to deliver electrical power to the one or more electrical components of the drug delivery device <NUM>. The power supply <NUM> can be a source of power which is integral to drug delivery device <NUM> and/or can be a mechanism configured to connect the drug delivery device <NUM> to an external source of power. The processor <NUM> is configured to receive gathered data from the sensor <NUM> and to cause the data to be stored in the memory <NUM>, to be indicated on the device indicator <NUM>, and/or and to be communicated externally via the communications interface <NUM>. The memory <NUM> is configured to store instructions that are configured to be executed by the processor <NUM> for the processor <NUM> to process information regarding the various electrical components with which the processor <NUM> is in communication.

As mentioned above, the drug delivery device <NUM> can include different features in different embodiments depending upon various requirements. For example, the drug delivery device <NUM> can omit any one or more of the depth guide <NUM>, the device indicator <NUM>, the sensor <NUM>, the communications interface <NUM>, the processor <NUM>, the memory <NUM>, and the power supply <NUM>.

<FIG> illustrate an exemplary embodiment of the drug delivery device <NUM> of <FIG>. <FIG> illustrate a drug delivery device <NUM> that includes a coupling mechanism <NUM> configured to releasably couple to a vial <NUM>. <FIG> illustrates the vial <NUM> releasably coupled to the drug delivery device <NUM>. <FIG> illustrates the vial <NUM> as a standalone element. The vial <NUM> is generally configured and used similar to the vial <NUM> of <FIG>. The vial <NUM> in this illustrated embodiment includes a base portion <NUM> and a head portion <NUM> that has a larger maximum outer diameter than then base portion <NUM>, though the vial <NUM> does not include a tapering neck portion. The vial <NUM> also includes a seal member at a proximal end thereof in the head portion <NUM>, although as mentioned above, in some embodiments, the seal member can be omitted.

The coupling mechanism <NUM> in this illustrated embodiment includes threading <NUM> on an external surface of a piston of the drug delivery device <NUM> that is configured to releasably thread with threading on an internal surface of the vial <NUM>. The vial's threading is obscured in <FIG>. The piston defines the coupling mechanism <NUM>. The coupling mechanism <NUM> can have other embodiments. For example, the coupling mechanism <NUM> can include a clip configured to releasably clip to the head portion <NUM> of the vial <NUM>. For another example, one of the coupling mechanism <NUM> and the vial <NUM> can include one or more protrusions extending therefrom configured to be releasably seated in one or more corresponding grooves or depressions formed in the other of the coupling mechanism <NUM> and the vial <NUM>. In some embodiments, the one of the coupling mechanism <NUM> and the vial <NUM> that includes the one or more protrusions can be configured to flex at least in an area in which the one or more protrusions are located to facilitate seating of the one or more protrusions in, and decoupling of the one or more protrusions from, the one or more corresponding grooves or depressions. In some embodiments, the one or more protrusions and the one or more corresponding grooves or depressions can be configured similar to a quarter-turn cam latch or lock.

A distal end 402d of the piston <NUM> is configured to puncture or pierce through the vial's seal member. In other words, as the vial <NUM> and the drug delivery device <NUM> are coupled, e.g., threaded, together, the piston <NUM> punctures or pierces through the vial's seal member. The vial <NUM> can thus be fluid tight until the vial <NUM> is coupled to the drug delivery device <NUM>, after which the drug contained in the vial <NUM> can flow out of the vial <NUM> for delivery. The distal end 402d of the piston <NUM> can include a sharp edge, e.g., around a perimeter of the piston's distal end 402d, to facilitate the puncturing or piercing of the vial's seal member or can otherwise include a feature configured to facilitate the puncturing or piercing, such as by having one or more sharp extensions extending distally therefrom. In some embodiments, the seal member can be omitted from the vial <NUM>, in which case the piston <NUM> need not be configured to puncture or pierce through the vial's seal member.

The drug delivery device <NUM> includes a body <NUM> in the form of a casing. The vial <NUM> is configured to move relative to the body <NUM> to cause delivery of the drug from the drug delivery device <NUM> through an opening <NUM> formed in a tip <NUM> of the body <NUM>. The tip <NUM> is configured to be inserted into a first nostril of the patient during a first stage of operation of the drug delivery device <NUM> and into a second nostril of the patient during a second stage of operation of the drug delivery device <NUM>. The vial <NUM> thus defines an actuator configured to be actuated to cause drug delivery to begin. The drug in this illustrated embodiment is configured to be self-administered such that the user who actuates the actuator, e.g., the vial <NUM>, is the patient receiving the drug from the drug delivery device <NUM>.

To allow the vial <NUM> to be actuated after being threaded to the piston <NUM> such that the vial <NUM> moves proximally relative to the piston <NUM>, the vial <NUM> is threaded proximally past the threading <NUM> on the piston <NUM>. The vial <NUM> can thereafter be pushed proximally to actuate the drug delivery device <NUM>. It will be appreciated that the terms "proximal" and "distal" are used herein with reference to a user gripping a nasal drug delivery device for drug delivery, with proximal indicating a direction toward the nose. However, drug delivery devices are used in many orientations and positions, and these spatial terms are not intended to be limiting and absolute.

The drug delivery device <NUM> does not need to be primed after the vial <NUM> has been releasably coupled thereto and prior to actuation of the drug delivery device <NUM> to cause drug delivery, which may ease use of the drug delivery device <NUM> by a user.

The body <NUM> has the piston <NUM> fixed thereto. From an inner end face of the piston <NUM> emanates an outlet channel <NUM>, which is guided in valve-free manner to the opening <NUM> leading into the open and which is formed by an atomizing nozzle. The outlet channel <NUM> becomes to be in fluid communication with the hollow interior of the vial <NUM> in response to the piston <NUM> puncturing or piercing the seal member of the vial <NUM>.

The body <NUM> includes a handle portion <NUM> configured to be handheld during coupling of the vial <NUM> and the drug delivery device <NUM> and during drug delivery. Flattened sides of the handle portion <NUM> include two facing finger openings <NUM> configured to receive a thumb of a user's hand with the index and middle finger of this hand on either side of a discharge connection <NUM> of the handle portion <NUM> on an outside of the handle portion's end wall <NUM> or elsewhere on the handle portion <NUM>. By moving together the thumb and the two other fingers the vial <NUM> can be displaced with respect to the piston <NUM> or the body <NUM> and the drug consequently sprayed out of the vial <NUM> through the discharge channel <NUM> and through the opening <NUM>. The handle portion <NUM>, as well as various other aspects of the drug delivery device <NUM>, are further described in <CIT>.

The discharge connection <NUM> includes a piston sleeve <NUM> constructed in one piece therewith and radially spaced within the discharge connection <NUM>. The piston sleeve <NUM> projects beyond the end wall <NUM> both outwards and inwards into the handle portion <NUM>. The piston sleeve <NUM> carries the piston <NUM> inserted therein. For this purpose the rear end of the piston <NUM> is extended to a piston shaft <NUM> constructed in one piece therewith and having substantially the same external cross-sections and which is set back with respect to the end face of the discharge connection <NUM> and with its associated end face engaging on an inner shoulder of the discharge connection <NUM> in such a way that a twisting device for the drug is formed between the end face and the discharge connection <NUM>. In the vicinity of the piston <NUM>, which only projects slightly beyond the piston sleeve <NUM>, the outlet channel <NUM> is formed by a central longitudinal bore which, immediately behind the end of the piston sleeve <NUM> located at the piston <NUM>, passes via a transverse bore into a main portion of the outlet channel <NUM>, which is defined between an outer circumference of the piston shaft <NUM> and an inner circumference of the piston sleeve <NUM> and which can, e.g., be formed by at least one longitudinal groove on the outer circumference of the piston shaft <NUM>.

A base plate at a distal end 404d of the vial <NUM> is curved inwards in such a way that it forms on its outside a thumb depression for the engagement of the thumb cap of the user's hand and on the inside has a correspondingly curved protuberance. A front end face of the piston <NUM> includes a depression that is shaped substantially identically to the protuberance and whose base face strikes against the cylinder base plate at the end of the complete pump stroke, so that virtually no residual quantity of the drug to be discharged remains in the vial <NUM> after actuation. The base plate is internal to the vial <NUM> and is thus obscured in <FIG>. In other embodiments, the base plate is linear instead of curved.

One actuation of the vial <NUM> causes the drug to be delivered into one nostril of the patient into which the tip <NUM> has been inserted. Proper delivery of the drug in one dosing session can, however, require the drug to be delivered into each of the patient's nostrils. As mentioned above, it is desired that an equal dose of the drug be delivered to each nostril to inhibit under-dosing of the drug.

In order to allow for two drug sprays from the drug delivery device <NUM>, the drug delivery device <NUM> includes a limiting device <NUM>. Omitting the limiting device <NUM> allows the drug delivery device <NUM> to be actuated only one time to deliver one drug spray.

The limiting device <NUM> includes a plurality of successive stops in the proximal or stroke direction and which can be one stop larger or smaller than the number of partial strokes, so that at least there is such a stop <NUM> for all the partial strokes before the last partial stroke. A counter-stop defined by a proximal surface 404p of the vial <NUM> is associated with the stop <NUM> and successively located stops. The stop <NUM> includes two facing stop faces <NUM> in the form of inner shoulders that are curved and with which is associated as the counter-stop. The stop faces <NUM> and/or the counter-stop has a ramp <NUM> extending over at least part of its width and the stop faces <NUM> can be constructed as a ramp.

The stop <NUM> is formed by a circumferentially divided, radially inwardly projecting resilient collar <NUM>, whose ring portions are in each case provided on a spring arm <NUM> freely projecting proximally in the direction of the pump stroke of the piston <NUM> or constructed in one piece therewith. In the illustrated embodiment there are two facing portions of the resilient collar <NUM> or spring arms <NUM> in the direction of the longer extension of the end wall <NUM> and are ring-segmental and whose ends are slightly set back with respect to the shallow curved longitudinal sides of the handle portion <NUM> and are consequently contact-free with respect to the body <NUM>. The spring arms <NUM> are also curved by an arc angle of substantially <NUM>° so that they form shell-shaped resilient, stable spring elements, which are relatively hard even in the case of relatively small wall thicknesses. The stop <NUM> or spring arms <NUM> form a component of a one-piece, muff-like stop body <NUM>, which at its end remote from the free ends of the spring arms <NUM> has a ring disk-like end wall <NUM> spaced from the stop <NUM> and which in the vicinity of the connection of discharge connection <NUM> to its outside engages on a ring shoulder of the body <NUM> formed by the inside of the end wall <NUM>. The stop body <NUM> is fixed by springing into a retaining clip <NUM>, which is constructed in one piece with the body <NUM> and is formed by two ring segmental clip jaws, which project from the inside of the end wall <NUM>. The clip jaws, which only engage around the stop body <NUM> in the vicinity of the spring arms <NUM> and also only over a small part of its length on the outside, are provided on their insides with in each case one ring groove or the like for the engagement of a locking bead <NUM>, which is provided roughly in the plane of the inside of the end wall <NUM> on the outer circumference of the stop body <NUM> and serves for the resilient, axially secured springing of the stop body <NUM> into the retaining clip <NUM>.

The stop <NUM> is spaced from the free ends of the spring arms <NUM>. Between the stop face <NUM> and the free ends directed against the vial <NUM> in an initial position before first actuation, the spring arms <NUM> form on their facing inner faces centering guides <NUM> for the vial <NUM>. The centering guides <NUM> are formed by an inner cone tapering in acute angled manner towards the stop face <NUM> and with which is associated as a counter-face an outer circumferential proximal edge of the open end of the vial <NUM>, e.g., at the head portion <NUM> thereof.

At the end of the first stage of operation, the counter-stop face strikes against the stop face <NUM>, so that a significant or at least noticeable resistance is exerted against further operation of the device <NUM>. If this resistance is overcome by a correspondingly more powerful operation, then as a result of the ramp the spring arms <NUM> are forced outwards until they slide on the outer circumference of the vial <NUM> with the inner circumferential surfaces of the vial <NUM> connected to the ramp <NUM>. Thus, on overcoming the stop face <NUM> the second stage of operation begins. At the end of the second stage of operation, the counter-stop face strikes against a further stop face <NUM> of the stop body <NUM>. The further stop face <NUM> is appropriately formed by the inside of the end wall <NUM> and arranged in such a way that simultaneously the front end face of the piston <NUM> strikes against the vial's bottom plate. The end wall <NUM> is traversed by the piston sleeve <NUM> or the piston rod, so that it can contribute to the positional stabilization thereof.

As mentioned above, the collar <NUM> is resilient. The collar's resiliency allows the collar <NUM> to flex distally (downwardly in the view of the device <NUM> illustrated in <FIG>) in response to the vial <NUM> being pulled distally to remove the vial <NUM> from the device <NUM> after doses of the drug have been delivered. The collar's resiliency also allows the collar <NUM> to flex proximally (upwardly in the view of the device <NUM> illustrated in <FIG>) to allow a second vial to be used with the device <NUM> similar to that discussed above regarding the vial <NUM>, and so on with one or more additional vials.

Embodiments of the drug delivery device <NUM> in the illustrated embodiment of <FIG> are not powered, e.g., does not include any electrical components such as a processor, a sensor, a memory, a communications interface, etc. The drug delivery device <NUM> thus need not include a power supply though a power supply could be included, e.g., for connectivity, for powering a light source of the drug delivery device, etc..

The drug delivery device <NUM>, as with every drug delivery device described herein as being configured to releasably couple to a vial, can be provided as part of a kit including a plurality of vials, e.g., two, three, four, five, six, seven, eight, nine, ten, etc., each configured to be successively releasably coupled to the drug delivery device <NUM>. Each of the plurality of vials can be provided without yet being coupled to the drug delivery device <NUM>, or one of the vials can be provided releasably coupled to the drug delivery device <NUM> with a remainder of the vials being provided without yet being coupled to the drug delivery device <NUM>. Each of the plurality of vials can include an order indicator thereon that indicates an order in which the vial should be releasably coupled to the drug delivery device <NUM>. For example, the order indicator can include a number printed on the vial, etched into the vial, printed on a label adhered to the vial, printed on a box or other package containing the vial therein, or otherwise made visible to a user of the vial. For another example, the order indicator can include a color on the vial, on a label on the vial, on a box or other package containing the vial therein, or otherwise made visible to a user of the vial. For yet another example, the order indicator can include a number and a color.

<FIG> illustrate another exemplary embodiment of the drug delivery device <NUM> of <FIG>. <FIG> illustrate a drug delivery device <NUM> that is configured and used similar to the drug delivery device <NUM> of <FIG> except that the drug delivery device <NUM> includes a device indicator <NUM> configured to present information to a user about a status of the drug delivery device <NUM>. The device indicator <NUM> in this illustrated embodiment is configured to indicate whether or not the vial <NUM> is releasably coupled to the drug delivery device <NUM>, e.g., is releasably coupled to a coupling mechanism <NUM> thereof. The device indicator <NUM> is a visual indicator, but as mentioned above the device indicator <NUM> can additionally or alternatively be an audio indicator configured to provide sound. The device indicator <NUM> is configured to indicate by color whether or not the vial <NUM> is releasably coupled to the drug delivery device <NUM>. <FIG> shows the device indicator <NUM> as having a first color that is indicative of no vial being releasably coupled to the drug delivery device <NUM>. <FIG> shows the device indicator <NUM> as having a second color that is different than the first color and that is indicative of the vial <NUM> being releasably coupled to the drug delivery device <NUM>.

The drug delivery device <NUM> includes a single device indicator <NUM> in this illustrated embodiment but can include a plural number of device indicators <NUM>. For example, a second device indicator <NUM> can be located on an opposite side of the drug delivery device <NUM> than the illustrated device indicator <NUM>.

The location of the device indicator <NUM> in <FIG> is shown as one example, as the device indicator <NUM> can be located in any of a variety of locations on the drug delivery device <NUM>.

The drug delivery device <NUM> includes a movable mechanism operatively coupled to the device indicator <NUM> to cause the device indicator <NUM> to change between its two color states. For example, the movable mechanism can include an elongate rod that extends longitudinally along the coupling mechanism <NUM> and the drug delivery device's piston shaft that is configured to be pushed upward by the vial <NUM> as the vial <NUM> is advanced proximally along the coupling mechanism <NUM> to releasably couple to the drug delivery device <NUM>. The elongate rod is spring biased or otherwise biased to a distal position such that when the vial <NUM> is removed from the drug delivery device <NUM>, the elongate rod automatically moves distally to change the device indicator <NUM> from the second color back to the first color.

<FIG> illustrate another exemplary embodiment of the drug delivery device <NUM> of <FIG>. <FIG> illustrates a drug delivery device <NUM> that includes a coupling mechanism <NUM> configured to releasably couple to a vial <NUM>. The coupling mechanism <NUM> in this illustrated embodiment includes a groove formed in the drug delivery device <NUM>, and the vial <NUM> includes a corresponding protrusion extending from the vial <NUM> that is configured to be releasably seated in the groove. <FIG> illustrates the vial <NUM> releasably coupled to the drug delivery device <NUM>. The vial <NUM> is generally configured and used similar to the vial <NUM> of <FIG>. The vial <NUM> in this illustrated embodiment includes a base portion and a head portion that has a larger maximum outer diameter than then base portion, and the vial <NUM> includes a tapering neck portion.

An opening <NUM> of the nasal spray device <NUM> through which the drug exits the nasal spray device <NUM> is formed in in a dispensing head <NUM> of the nasal spray device <NUM> in a tip <NUM> of the dispensing head <NUM>. The dispensing head <NUM> includes a depth guide <NUM>. In an exemplary embodiment, the tip <NUM> is configured to be inserted into a first nostril of the patient during a first stage of operation of the nasal spray device <NUM> and into a second nostril of the patient during a second stage of operation of the nasal spray device <NUM>. The first and second stages of operation involve two separate actuations of the nasal spray device <NUM>, a first actuation corresponding to a first dose of the drug being delivered and a second actuation corresponding to a second dose of the drug being delivered. In some embodiments, the nasal spray device <NUM> is configured to be actuated only once to deliver one nasal spray. In some embodiments, the nasal spray device <NUM> is configured to be actuated three or more times to deliver three or more nasal sprays, e.g., four, five, six, seven, eight, nine, ten, etc..

In this illustrated embodiment, the dispensing head <NUM> has a tapered shape in which the dispensing head <NUM> has a smaller diameter at its distal end than at its proximal end where the opening <NUM> is located. A spray chamber <NUM> through which the drug is configured to pass before exiting the opening <NUM> is located within a proximal portion of the tapered dispensing head <NUM>, distal to the opening <NUM>. When the drug passes through the spray chamber <NUM> at speed, the spray chamber <NUM> facilitates production of a fine mist that exits through the opening <NUM> with a consistent spray pattern. Arrow <NUM> illustrates a path of travel of the drug from the vial <NUM> and out of the opening <NUM>.

In some embodiments, the dispensing head <NUM> can include two tips <NUM> each having an opening <NUM> therein such that the nasal spray device <NUM> is configured to simultaneously deliver doses of drug into two nostrils in response to a single actuation.

The dispensing head <NUM> is configured to be pushed toward the vial <NUM>, e.g., depressed by a user pushing down on the depth guide <NUM>, to actuate the nasal spray device <NUM>. In other words, the dispensing head <NUM> is configured as an actuator to be actuated to drive the drug from the vial <NUM> and out of the nasal spray device <NUM>. In an exemplary embodiment, the nasal spray device <NUM> is configured to be self-administered such that the user who actuates the nasal spray device <NUM> is the patient receiving the drug from the nasal spray device <NUM>, although another person can actuate the nasal spray device <NUM> for delivery into another person.

The actuation, e.g., depressing, of the dispensing head <NUM> is configured to cause venting air to enter the vial <NUM>, as shown by a second arrow <NUM>. The air entering the vial <NUM> displaces drug in the drug holder through a tube <NUM> and then into a metering chamber <NUM>, which displaces drug proximally through a cannula <NUM>, through the spray chamber <NUM>, and then out of the opening <NUM>. In response to release of the dispensing head <NUM>, e.g., a user stops pushing downward on the dispensing head <NUM>, a bias spring <NUM> causes the dispensing head <NUM> to return to its default, resting position to position the dispensing head <NUM> relative to the vial <NUM> for a subsequent actuation and drug delivery.

<FIG> illustrates another exemplary embodiment of the drug delivery device <NUM> of <FIG>. <FIG> illustrates a drug delivery device <NUM> that is configured and used similar to the drug delivery device <NUM> of <FIG> except that the drug delivery device <NUM> includes a coupling mechanism <NUM> that includes a cavity configured to receive the vial <NUM> therein. The coupling mechanism <NUM> also includes a piston located at least partially within the cavity that the vial <NUM> is configured to releasably engage within the cavity similar to that discussed above regarding the coupling mechanism <NUM>. The coupling mechanism <NUM> being located within the drug delivery device <NUM> instead of extending therefrom, as in the embodiment of <FIG>, may help protect the coupling mechanism <NUM> from being damaged in transit and/or storage. For example, the coupling mechanism <NUM> can include threading on an internal surface thereof configured to releasably thread with threading on an external surface of the vial <NUM>. For another example, the coupling mechanism <NUM> can include a clip configured to releasably clip to the head portion <NUM> of the vial <NUM>. For yet another example, one of the coupling mechanism <NUM> and the vial <NUM> can include one or more protrusions extending therefrom configured to be releasably seated in one or more corresponding grooves or depressions formed in the other of the coupling mechanism <NUM> and the vial <NUM>.

The drug delivery device <NUM> can include a device indicator similar to the device indicator <NUM> discussed above with respect to <FIG> and <FIG>.

In some embodiments, a plurality of vials each configured to be releasably coupled to a drug delivery device can be pre-loaded on a cartridge strip. Each of the vials is configured to be sequentially released from the cartridge strip for releasable coupling to the drug delivery device, as described herein. Pre-loading the vials on the cartridge strip may help a user know the correct order in which to couple to the vials to the drug delivery device because the vials can be lined up on the cartridge strip and simply be coupled to the drug delivery device in line order. In addition to or instead of the vials each including an order indicator, the cartridge strip can include an order indicator thereon that indicates an order in which the vials should be releasably coupled to a drug delivery device to provide further indication of vial order use. Pre-loading the vials on the cartridge strip may help a user comply with a prescribed dosing schedule and/or prescribed dosage amount, similar to a pill box with different compartments for each day's prescribed pills, because the cartridge strip of vials can provide a simple visible verification to a user of how many vials have already been coupled to the drug delivery device for use and how many vials have not yet been coupled to the drug delivery device for use. Pre-loading the vials on the cartridge strip may help prevent any of the vials from being lost before being coupled to the drug delivery device since the vials are all attached together via the cartridge strip.

<FIG> illustrates one embodiment of a cartridge strip <NUM> releasably coupled to a plurality of vials <NUM>. Each of the vials <NUM> is generally configured and used similar to the vial <NUM> of <FIG>. Six vials <NUM> are coupled to the cartridge strip <NUM> in this illustrated embodiment, but another number of vials <NUM> can be so coupled, e.g., two, three, four, five, seven, eight, nine, ten, etc..

<FIG> also illustrates another exemplary embodiment of the drug delivery device <NUM> of <FIG>. <FIG> illustrates a drug delivery device <NUM> that is configured and used similar to the drug delivery device <NUM> of <FIG>. Opposed inner surfaces <NUM> of the drug delivery device's handle portion <NUM> serve as an alignment member configured to align the drug delivery device <NUM> relative to cartridge strip <NUM> by contacting the cartridge strip <NUM> so one of the vials <NUM> can be released from the cartridge strip <NUM> and releasably coupled to the drug delivery device <NUM> in proper alignment therewith, e.g., coupled to and in alignment with a coupling mechanism <NUM> of the drug delivery device <NUM>. Arrow <NUM> indicates the proximal direction in which the vials <NUM> are sequentially moved into releasable coupling with the drug delivery device <NUM> by manual pushing of the one of the vials <NUM> that is aligned with the coupling mechanism <NUM>. The coupling mechanism <NUM> can include, for example, a clip configured to releasably clip to the vial <NUM> when the vial <NUM> is pushed into engagement with the clip. For another example, one of the coupling mechanism <NUM> and the vial <NUM> can include one or more protrusions extending therefrom configured to be releasably seated in one or more corresponding grooves or depressions formed in the other of the coupling mechanism <NUM> and the vial <NUM> when the vial <NUM> has been pushed enough to cause engagement of the one or more protrusions and one or more corresponding grooves or depressions.

The drug delivery device <NUM> can be released from contact with the cartridge strip <NUM> before actuating the drug delivery device <NUM>, e.g., before the vial <NUM> that is releasably coupled to the drug delivery device <NUM> is pushed proximally. For at least some users, the drug delivery device <NUM> can be released from the cartridge strip <NUM> before actuating the drug delivery device <NUM> may make the drug delivery device <NUM> easier to hold during drug delivery. Alternatively, the drug delivery device <NUM> can be coupled to the cartridge strip <NUM> during the actuation of the drug delivery device <NUM>, e.g., when the vial <NUM> that is releasably coupled to the drug delivery device <NUM> is pushed proximally. The drug delivery device <NUM> remaining coupled to the cartridge strip <NUM> during drug delivery may make it easier and/or faster for a user to deliver drug from multiple ones of the vials, such as if a first vial is used to spray drug into one nostril of a patient and a second vial is used to spray drug into the patient's other nostril. The drug delivery device <NUM> remaining coupled to the cartridge strip <NUM> during drug delivery may help prevent inadvertent loss of one or the other of the drug delivery device <NUM> and the cartridge strip <NUM> if one or more of the vials <NUM> are used at different dosing times from one another, e.g., at a prescribed time separation between doses.

In some embodiments, the drug delivery device <NUM> can be non-releasably coupled to the cartridge strip <NUM>, which may make it easier and/or faster for a user to deliver drug from multiple ones of the vials and/or may help prevent inadvertent loss of one or the other of the drug delivery device <NUM> and the cartridge strip <NUM> if one or more of the vials <NUM> are used at different dosing times from one another. After all of the vials <NUM> have been used, e.g., after drug has been delivered therefrom using the drug delivery device <NUM>, the used vials <NUM> and the drug delivery device <NUM> can be disposed of as medical waste in whole or in part or by recycling in whole or in part. Non-releasable coupling of the cartridge strip <NUM> and the drug delivery device <NUM> can be achieved in any of a variety of ways. For example, the cartridge strip <NUM> can have an elongate longitudinal channel formed in a side thereof, and the drug delivery device <NUM> can include at least one protrusion extending radially outward from the handle portion <NUM> that is configured to slide within the channel as the drug delivery device <NUM> is moved along the cartridge strip <NUM> to align with the different vials <NUM>. Alternatively, the cartridge strip <NUM> can include the at least one protrusion, and the drug delivery device can include the elongate longitudinal channel. For another example, the handle portion <NUM> of the drug delivery device <NUM> can define an enclosed shape, with the opposed inner surfaces <NUM> defining at least a portion of the shape's perimeter, within which the cartridge strip <NUM> is located.

Each of the vials <NUM> in the embodiment of <FIG> includes a removable protective member or stopper <NUM> that is configured to be removed just prior to the vial <NUM> being releasably coupled to the drug delivery device <NUM>, although as discussed above the vial <NUM> may omit the protective member or stopper <NUM>.

<FIG> illustrates another embodiment in which each of a plurality of vials <NUM> releasably coupled to a cartridge strip <NUM> do not include a removable protective member or stopper but do include a seal member <NUM> at a proximal end thereof. Each of the vials <NUM> is generally configured and used similar to the vial <NUM> of <FIG>. The cartridge strip <NUM> is generally configured and used similar to the cartridge strip <NUM> of <FIG>. Two vials <NUM> are coupled to the cartridge strip <NUM> in this illustrated embodiment, but another number of vials <NUM> can be so coupled, e.g., three, four, five, six, seven, eight, nine, ten, etc..

<FIG> illustrate another embodiment in which each of a plurality of vials <NUM> are releasably coupled to a cartridge strip <NUM>. Each of the vials <NUM> is generally configured and used similar to the vial <NUM> of <FIG>. The cartridge strip <NUM> is generally configured and used similar to the cartridge strip <NUM> of <FIG>. Four vials <NUM> are coupled to the cartridge strip <NUM> in this illustrated embodiment, but another number of vials <NUM> can be so coupled, e.g., two, three, five, six, seven, eight, nine, ten, etc..

<FIG> also illustrate a drug delivery device <NUM> that is configured and used similar to the drug delivery device <NUM> of <FIG>. Opposed inner surfaces 904i of the drug delivery device's handle portion <NUM> serve as an alignment member configured to align the drug delivery device <NUM> relative to cartridge strip <NUM> so one of the vials <NUM> can be released from the cartridge strip <NUM> and releasably coupled to the drug delivery device <NUM> in proper alignment therewith, e.g., coupled to and in alignment with a coupling mechanism of the drug delivery device <NUM>.

As shown in <FIG>, the cartridge strip <NUM> includes a pair of detents <NUM> on opposed longitudinal sides of the cartridge strip <NUM> that is associated with each of the vials <NUM>. In other words, the cartridge strip <NUM> in this illustrated embodiment includes four pairs of detents <NUM>, one pair for each of the four vials <NUM>. Each one of the vials <NUM>, when coupled to the cartridge strip <NUM>, is positioned between its associated pair of detents <NUM>. Each pair of detents <NUM> serves as an alignment mechanism configured to cooperate with the alignment member of the drug delivery device <NUM> to align the drug delivery device <NUM> relative to the cartridge strip <NUM> so one of the vials <NUM> can be released from the cartridge strip <NUM> and releasably coupled to the drug delivery device <NUM> in proper alignment therewith. Each pair of detents <NUM> is configured to engage the opposed inner surfaces 904i of the drug delivery device <NUM>, as shown in <FIG>. The engagement of the two detents <NUM> with the drug delivery device <NUM> allows the drug delivery device <NUM> to be properly aligned relative to cartridge strip <NUM> for vial <NUM> coupling. The detents <NUM> and the opposed inner surfaces 904i have complementary sizes and shapes to facilitate engagement therebetween.

The cartridge strip <NUM> includes a plurality of perforations <NUM> that each extend substantially perpendicular to a longitudinal axis <NUM> of the cartridge strip <NUM>. A person skilled in the art will appreciate that the perforations <NUM> may not extend precisely perpendicular to the longitudinal axis <NUM> but nevertheless be considered to be substantially perpendicular thereto due to any number of factors, such as manufacturing tolerances and sensitivity of measurement equipment. A number of the perforations <NUM> is one less than a number of vials <NUM> that can be coupled to the cartridge strip <NUM>. The cartridge strip <NUM> in this illustrated embodiment thus includes three perforations <NUM>, which is one less than the four vials <NUM>. The perforations <NUM> are configured to allow for tearing of the cartridge strip <NUM> therealong. After one of the vials <NUM> has been coupled to the drug delivery device <NUM> and removed from the cartridge strip <NUM>, the cartridge strip <NUM> can be torn along the one of the perforations <NUM> adjacent to the vial's original coupling location with the cartridge strip <NUM> and nearest a free end of the cartridge strip <NUM>. For example, perforation 910a labeled in <FIG> indicates the perforation <NUM> that can be torn after the right-most vial <NUM> has been coupled to the drug delivery device <NUM> and removed from the cartridge strip <NUM>. The cartridge strip <NUM> can be torn at a perforation <NUM> without the vial <NUM> coupled to the cartridge strip <NUM>, or the perforation <NUM> can be torn with the vial <NUM> re-coupled to the cartridge strip <NUM> after having been coupled to and used with the drug delivery device <NUM>.

The cartridge strip <NUM> includes an opening <NUM> therein for each of the vials <NUM> and includes a pair of tabs <NUM> that extends radially inward into each of the openings <NUM>. In other words, the cartridge strip <NUM> in this illustrated embodiment includes four openings <NUM> and four pairs of tabs <NUM>, one opening and one pair for each of the four vials <NUM>. Each one of the vials <NUM>, when coupled to the cartridge strip <NUM>, is engaged with one of the pairs of tabs <NUM>. Each pair of tabs <NUM> serves as a coupling feature configured to cooperate with a coupling mechanism of its associated vial <NUM> to releasably couple the vial <NUM> to the cartridge strip <NUM>. The coupling mechanism of each vial <NUM> includes a rib <NUM> in a head portion of the vial <NUM>. The rib <NUM> is configured to releasably seat the tabs <NUM> therein, as shown in <FIG>. The rib <NUM> extends circumferentially around the vial's head portion, which may facilitate coupling of the vial <NUM> at any rotational orientation relative to the cartridge strip <NUM>. Each of the vials <NUM> also includes a coupling mechanism configured to couple the vial <NUM> to the drug delivery device <NUM>, as discussed herein.

In this illustrated embodiment, the cartridge strip <NUM> is resilient. The cartridge strip's resiliency allows the cartridge strip <NUM> to flex to facilitate coupling each of the vials <NUM> with a drug delivery device <NUM>. The cartridge strip <NUM> is made of one or more materials that facilitate the flexing of the cartridge strip <NUM>, such as the cartridge strip <NUM> being made of at least one plastic. In this illustrated embodiment, the entire cartridge strip <NUM> is resilient. In other embodiments, only a portion of the cartridge strip <NUM> is resilient. Only a portion of the cartridge strip <NUM> being resilient with a remainder of the cartridge strip <NUM> being rigid and not resilient may facilitate user handling of the cartridge strip <NUM> at least during coupling of the vials <NUM> with the drug delivery device <NUM>. For example, the tabs <NUM> can be resilient with a remainder of the cartridge strip <NUM> not being resilient. In such embodiments the cartridge strip <NUM> lacks the perforations <NUM>. For another example, the tabs <NUM> and areas adjacent each of the perforations <NUM> can be resilient with a remainder of the cartridge strip <NUM> not being resilient.

In an exemplary embodiment of using the cartridge strip <NUM>, the drug delivery device <NUM> is positioned relative to the cartridge strip <NUM> with the drug delivery device's opposed inner surface 904i engaging one of the cartridge strip's pair of detents <NUM>, as shown in <FIG>. The drug delivery device <NUM> is thereby properly aligned with one of the vials <NUM> for coupling. The one of the vials <NUM> is then releasably coupled to the drug delivery device <NUM>. As shown in <FIG>, a user can position two fingers <NUM> on a proximal surface of the drug delivery device's handle portion <NUM> and a thumb <NUM> on a distal surface 900d of the one of the vials <NUM>. Then, as shown in <FIG>, the user can push the vial <NUM> proximally with their thumb <NUM> while holding the drug delivery device <NUM> steady with their fingers <NUM> to couple the vial <NUM> to the drug delivery device <NUM> and cause delivery of a drug <NUM> from the vial <NUM> and out of the drug delivery device <NUM>. The drug delivery device <NUM> remains engaged with the detents <NUM> during delivery of the drug <NUM>. The vial <NUM> includes a distal flange 900b configured to facilitate a user's proximal pushing of the vial <NUM> by providing an enlarged surface area for the user's thumb <NUM> to push against.

After the drug <NUM> has been delivered from the drug delivery device <NUM>, the vial <NUM> can be re-coupled to the cartridge strip <NUM> with the rib <NUM> again engaging the tabs <NUM>. As shown in <FIG>, the vial <NUM> can be pulled distally relative to the drug delivery device <NUM> and the cartridge strip <NUM> to re-couple the ribs <NUM> and the tabs <NUM>. The vial's distal flange 900b is also configured to facilitate a user's grip of the vial's distal end to facilitate the user pulling the vial <NUM> distally. The drug delivery device <NUM> can then be repositioned relative to the cartridge strip <NUM> in engagement with another pair of detents <NUM> to prepare the drug delivery device <NUM> to be coupled to and used with another one of the vials <NUM>, as shown in <FIG>. Each of the remaining vials <NUM> can be similarly coupled to and used with the drug delivery device <NUM>.

The vial <NUM> can include a hollow interior within a base portion of the vial that includes a single chamber containing the drug <NUM> therein similar to the vial <NUM> of <FIG>, as in the illustrated embodiment of <FIG>. Alternatively, a hollow interior in a base portion of the vial <NUM> can include two chambers. <FIG> illustrates an exemplary embodiment of the vial <NUM> as a vial 900a including two chambers.

As shown in <FIG>, a base portion of the vial 900a defines a distal cavity 926a and a proximal cavity 928a. Air 930a is contained in the distal cavity 926a, and a drug 924a is contained in the proximal cavity 928a. In this way, the drug 924a can exit the vial 900a for delivery to a user followed by exit of the air 930a from the vial 900a for delivery to the user. The air 903a exiting the vial 900a after the drug 924a may help ensure that substantially all of the drug 924a has exited the drug holder 900a such that substantially no residual drug remains in the drug holder 900a. A person skilled in the art will appreciate that the amount of residual drug may not be precisely zero but nevertheless be considered to be substantially none due to any number of factors, such as sensitivity of measurement equipment. Having substantially no residual drug left in a vial after use thereof may prevent access to the drug after use of the vial, which may be particularly important for esketamine, ketamine, and other controlled substances that could be abused and/or be more likely than other drugs to lead to an addiction. Having substantially no residual drug left in a vial after use thereof may facilitate recycling of the used vial (alone or in combination with all of part of a drug delivery device that delivered drug from the vial) since substantially no drug will be present when the vial is recycled. Some drugs, such as esketamine, ketamine, and other controlled substances, may be required to be disposed of per the drug's Risk Evaluation and Mitigation Strategies (REMS) to help, e.g., ensure that the drug is not accessed by an unauthorized person. Disposal of the used vial can include recycling or throwing out the used vial (alone or in combination with all of part of a drug delivery device that delivered drug from the vial) as medical waste. Having substantially no residual drug left in a vial after use thereof may help satisfy the REMS since the vial will be substantially free of the drug when the vial is disposed.

The vial 900a includes a first seal member 932a configured to provide a fluid tight seal at a proximal end of the proximal cavity 928a such that the drug 924a is contained in the proximal cavity 928a in the vial 900a until the seal provided by the first seal member 932a is broken. The first seal member 932a is located in the base portion of the vial 900a in this illustrated embodiment but can instead be located in a head portion of the vial 900a. The seal provided by the first seal member 932a can be broken in a variety of ways, such as by being pierced by a needle, pin, piston, etc. of the drug delivery device to which the vial 900a is coupled. The first seal member 932a can have a variety of configurations, as will be appreciated by a person skilled in the art, such as by being a pierceable polymer septum or a foil layer. The first seal member 932a can be protected from accidental puncturing or piercing before intended use with a removable protective member or stopper, such as a TE seal, etc. located at the proximal end of the vial <NUM>.

The distal and proximal cavities 926a, 928a are isolated from one another in an initial state of the vial 900a. The vial 900a includes a second seal member 934a that is located in the base portion. The second seal member 934a is configured to provide a fluid tight seal such that the air 930a in the distal cavity 926a and the drug 924a in the proximal cavity 928a are separated from each other until the seal provided by the second seal member 934a is broken. The seal provided by the second seal member 934a can be broken in a variety of ways, such as by being pierced by a needle, pin, piston, etc. of the drug delivery device to which the vial 900a is coupled, such as the same needle, pin, piston, etc. that breaks the first seal member 932a. The second seal member 934a can have a variety of configurations, as will be appreciated by a person skilled in the art, such as by being a pierceable polymer septum or a foil layer.

The first seal member 932a is proximal to both of the distal and proximal cavities 926a, 928a. The second seal member 934a is located between the distal and proximal cavities 926a, 928a, e.g., is distal to the proximal cavity 928a and is proximal to the distal cavity 926a, such that the distal and proximal cavities 926a, 928a are isolated from each other prior to piercing or puncturing of the second seal member 934a.

Embodiments of nasal drug delivery devices disclosed herein can be designed to be disposed of after a single use, or they can be designed to be used multiple times. In either case, in at least some embodiments, the drug delivery device can be reconditioned for reuse after at least one use. Reconditioning can include any combination of the steps of disassembly of the drug delivery device, followed by cleaning or replacement of particular pieces and subsequent reassembly. In particular, the drug delivery device can be disassembled, and any number of the particular pieces or parts of the drug delivery device can be selectively replaced or removed in any combination. Upon cleaning and/or replacement of particular parts, the drug delivery device can be reassembled for subsequent use either at a reconditioning facility, or by a health care provider immediately prior to use. A person skilled in the art will appreciate that reconditioning of a drug delivery device can utilize a variety of techniques for disassembly, cleaning/replacement, and reassembly. Use of such techniques, and the resulting reconditioned drug delivery device, are all within the scope of the present application.

Claim 1:
A drug delivery device (<NUM>, <NUM>, <NUM>, <NUM>) comprising:
a tip (<NUM>) configured to be positioned in a nose of a patient, the tip having an opening (<NUM>) therein;
a coupling mechanism (<NUM>,<NUM>,<NUM>) configured to releasably couple to a first vial (<NUM>,<NUM>, <NUM>,<NUM>) containing a first drug therein, to release the first vial therefrom, and to subsequently be releasably coupled to a second vial containing a second drug therein;
a plunger (<NUM>) configured to be actuated in a stroke direction through a first partial stroke and a second partial stroke to cause the first drug to exit through the opening, and to be subsequently actuated in the stroke direction through the first partial stroke and the second partial stroke to cause the second drug to exit through the opening;
characterized in that the drug delivery device further comprises:
a limiting device (<NUM>) comprising:
a one-piece stop body (<NUM>);
a plurality of spring arms (<NUM>) freely projecting in the stroke direction from the stop body and forming a component of the stop body;
a stop (<NUM>) formed by a circumferentially divided, radially inwardly projecting resilient collar (<NUM>), portions of which are in each case provided on each of the plurality of spring arms (<NUM>), the stop including a plurality of facing stop faces (<NUM>,<NUM>) in the form of an inner shoulder of the resilient collar (<NUM>); and
wherein the stop face is configured such that in use a counter-stop defined by a proximal surface (404p) of the first or second vial at the end of the first partial stroke strikes against the stop face (<NUM>), so that a noticeable resistance is exerted against further operation of the device, and
wherein the spring arms (<NUM>) are configured to be forced outwards until they slide on the outer circumference of the first or second vial, thereby allowing the resistance to be overcome by a correspondingly more powerful actuation.