Devices and methods for delivering dry powder medicaments

An apparatus includes a first member coupled to a second member. The first member defines a chamber containing a dry powder and includes a chamber wall that forms an outer boundary of the chamber. The second member includes a surface covering the chamber and defines an intake channel and an exit channel. The exit channel is fluidically coupled to the chamber via an exit opening. The intake channel is fluidically coupled to the chamber via an intake port. A center line of the intake channel is tangential to a portion of the chamber wall such that a portion of an inlet airflow conveyed into the chamber via the intake channel has a rotational motion. The intake port is defined at least in part by an intake ramp. The intake ramp includes a transition surface that forms an exit angle with respect to the surface of less than 105 degrees.

BACKGROUND

The embodiments described herein relate generally to medical devices and pharmaceutical compositions, and more particularly to drug products for delivery of dry powder medicaments.

Pressurized metered dose inhalation devices (pMDI) are well-known for delivering drugs to patients by way of their lungs. pMDI's are comprised of a pressurized propellant canister with a metering valve housed in a molded actuator body with integral mouthpiece. This type of inhalation device presents drug delivery challenges to patients, requiring significant force to actuate with inhalation and timing coordination to effectively receive the drug. pMDI's containing suspended drug formulations also have to be shaken properly by the patient prior to actuating to receive an effective dose of the drug. These relatively complicated devices also require priming due to low drug content in initial doses and can require cleaning by the patient. In some devices, an additional spacer apparatus is prescribed along with the pMDI to compensate for the timing coordination issue, thus creating additional complications related to the patient for, cleaning, storage and transport of the bulky spacer apparatus. While many patients are experienced operating pMDI's or pMDI's with spacers, new patients often experience a relatively significant learning curve to operate these devices properly.

Dry powder inhalation devices (DPI) are also well-known for delivering powderized drugs to the lungs. DPI technologies are either active involving external energy to break-up and aerosolize particles or, passive utilizing the patient's inspiratory energy to entrain and deliver the powder to the lungs. Some DPI technologies integrate electronics while others are fully mechanical. The powder drug storage formats are normally reservoir, individually pre-metered doses, or capsule based systems. Some known DPI devices include (or deliver) engineered drug particles, but in most known devices deliver a conventional blend of sized active pharmaceutical ingredient(s) (API) plus sized lactose monohydrate used as a bulking agent to aid in the powder filling process and as carrier particles to aid in delivery of the active pharmaceutical ingredient(s) to the patient. These API—lactose monohydrate blends among others require a means to break-up aggregates formed by attractive forces holding them together.

Some known devices for storing and delivering known dry powder formulations include a storage reservoir and a separate chamber within which the dry powder can be disaggregated in preparation for delivery to the patient. Such known systems, however, often include multiple pathways (e.g., from the reservoir to the preparation chamber), and thus can have diminished accuracy of the delivered dose due to undesired contact with pathway walls, inconsistency in withdrawing the dose from the reservoir, and the like.

Some known devices for storing and delivering known dry powder formulations rely, at least in part, on air flow produced by the patient inspiration (i.e., inhalation). Variation in the flow rates and velocities produced among the patient population, however, can cause variation in the delivered dose and/or fine particle fraction. Moreover, normal part-to-part variation, as well as variation caused during use (e.g., deformation or blocking of flow paths due to the patient gripping the device) can also lead to undesired variation in the airflow resistance and accuracy of the delivered dose, as well as the magnitude of fine particle fraction.

Additionally, some known dry powder delivery devices are susceptible to inconsistent performance resulting from variations in how different users interact with the device. Said another way, known dry powder delivery devices do not account for “human factors” in operation. For example, known dry powder delivery devices can be susceptible to variations in performance based on any one or all the following: tilting of the device (before or during use), failure to generate adequate flow and pressure drop (vacuum or negative pressure), failure by the user to actuate mechanisms completely and properly (and in the correct order), and failure to load drug cartridges, capsules or blisters properly. As one example, some known dry powder delivery devices include passageways that can be obstructed if a user inadvertently covers an inlet port or squeezes the body of the device with too much force.

Thus, a need exists for improved methods and devices for delivering dry powder drugs. Specifically, a need exists for a dry powder delivery device having improved accuracy, improved fine particle fraction, and ease of use and administration. A need also exists for improved methods of filling and assembling dry powder delivery devices.

SUMMARY

Medicament delivery devices, drug products and methods for administration of dry powder medicaments are described herein. In some embodiments, an apparatus includes a first member and a second member coupled to the first member. The first member defines at least a portion of a disaggregation chamber containing a dry powder and includes a chamber wall that forms an outer boundary of the disaggregation chamber. The second member includes a surface covering the disaggregation chamber and defines an intake channel and an exit channel. The exit channel is configured to be fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the second member. The intake channel is configured to be fluidically coupled to the disaggregation chamber via an intake port. A center line of a portion of the intake channel is tangential to a portion of the chamber wall of the first member such that a portion of an inlet airflow conveyed into the disaggregation chamber via the intake channel has a rotational motion about a center axis of the disaggregation chamber. The intake port is defined at least in part by an intake ramp. The intake ramp includes a transition surface that forms an exit angle with respect to the surface of less than 105 degrees.

In some embodiments, an apparatus includes a lower member and an upper member coupled to the lower member. The lower member defines at least a lower portion of a disaggregation chamber containing a dry powder. The lower member includes a raised surface along a center axis of the disaggregation chamber. The upper member includes a surface that encloses the disaggregation chamber and defines an upper portion of the disaggregation chamber, the upper member defines an intake channel and an exit channel. The intake channel is fluidically coupled to the disaggregation chamber via an intake opening, and the exit channel is fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the upper member. The exit opening is along the center axis. The upper member includes a protrusion extending from the surface, the protrusion in contact with the raised surface to maintain a distance between the raised surface and the exit opening.

DETAILED DESCRIPTION

Medicament delivery devices, drug products, and methods for administration of dry powder medicaments are described herein. In some embodiments, an apparatus includes a first member and a second member coupled to the first member. The first member defines at least a portion of a disaggregation chamber containing a dry powder and includes a chamber wall that forms an outer boundary of the disaggregation chamber. The second member includes a surface covering the disaggregation chamber and defines an intake channel and an exit channel. The exit channel is configured to be fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the second member. The intake channel is configured to be fluidically coupled to the disaggregation chamber via an intake port. A center line of a portion of the intake channel is tangential to a portion of the chamber wall of the first member such that a portion of an inlet airflow conveyed into the disaggregation chamber via the intake channel has a rotational motion about a center axis of the disaggregation chamber. The center line can be tangential in one plane (e.g., a top view) and non-tangential in other planes (e.g., a side view). The intake port is defined at least in part by an intake ramp. The intake ramp includes a transition surface that forms an exit angle with respect to the surface of less than 105 degrees.

Similarly stated, the transition surface is such that a second portion of the inlet airflow enters the disaggregation chamber at a flow angle of at least about 75 degrees (measured along the center line of the portion of the intake channel). In some embodiments, the transition surface is parallel to the center axis of the disaggregation chamber (or is normal to the surface of the second member). The structure of the transition surface advantageously produces a sudden expansion into the disaggregation chamber, which causes the second portion of the inlet airflow to recirculate or “fan out” in one or more directions that are not tangential to the chamber wall. This arrangement produces improved disaggregation and/or clearance of the dry powder and mixing of the particles within the airflow.

In some embodiments, the apparatus can further include a strip between the first member and the second member that retains the dry powder within the portion of the disaggregation chamber. In this manner, the disaggregation chamber can function both as a storage chamber and a disaggregation chamber that ensures the desired delivery characteristics of the powder stored therein. The strip fluidically isolates the portion of the disaggregation chamber from the intake channel and the exit channel when the strip is in a first position. The strip is configured to be moved relative to the first member to a second position to place the portion of the disaggregation chamber in fluid communication with the intake channel and the exit channel.

In some embodiments, an apparatus includes a first member and a second member coupled to the first member. The first member defines at least a portion of a disaggregation chamber containing a dry powder and includes a chamber wall that forms an outer boundary of the disaggregation chamber. The second member includes a surface covering the disaggregation chamber and defines an intake channel and an exit channel. The exit channel is fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the second member. The intake channel is configured to be fluidically coupled to the disaggregation chamber via an intake port. A center line of the intake channel is tangential to a portion of the chamber wall of the first member such that a first portion of an inlet airflow conveyed into the disaggregation chamber via the intake channel has a rotational motion about the exit opening. The center line can be tangential in one plane (e.g., a top view) and non-tangential in other planes (e.g., a side view). The intake port defined at least in part by an intake ramp that is ramp curved outwardly towards the chamber wall such that a second portion of the inlet airflow conveyed into the disaggregation via the intake channel is conveyed towards the chamber wall.

In some embodiments, the first member and the second member can be monolithically constructed.

In some embodiments, the intake ramp defines a first radius of curvature within a first plane normal to a center axis and a second radius of curvature within a second plane normal to the first plane. The first radius of curvature and the second radius of curvature each open outwardly towards the chamber wall. This arrangement causes a portion of the flow entering the disaggregation chamber (i.e., the second portion) to cross the path of the rotational flow within the disaggregation chamber (i.e., the first portion). This produces disruption of the rotational flow and dispersion of particles circulating in the rotational flow stream toward the outlet hole. Thus, this arrangement produces reduced dose release time and higher emitted dose percentage.

In some embodiments, an apparatus includes a first member and a second member coupled to the first member. The first member defines at least a portion of a disaggregation chamber containing a dry powder and includes a chamber wall that forms a boundary of the disaggregation chamber. The second member includes an inner surface and an outer surface and defines an intake channel and an exit channel. The inner surface covers the disaggregation chamber. The exit channel is fluidically coupled to the disaggregation chamber via an exit opening defined by the inner surface of the second member. The intake channel is fluidically coupled to the disaggregation chamber via an intake port. The intake channel fluidically coupled to an external volume outside of the disaggregation chamber by an external opening defined by the outer surface. The outer surface includes one or more barrier surfaces at least partially surrounding the external opening and that are configured to limit obstruction of the external opening.

In some embodiments, the barrier surfaces are formed from a set of protrusions extending from the outer surface of the second member. In some embodiments, the barrier surfaces are non-planar surface (or collectively form a set of non-planar surfaces). This arrangement can reduce the likelihood that a user's finger or other object will obstruct the external opening.

In some embodiments, an apparatus includes a lower member and an upper member coupled to the lower member. The lower member defines at least a lower portion of a disaggregation chamber containing a dry powder. The lower member includes a raised surface along a center axis of the disaggregation chamber. The upper member includes a surface that encloses the disaggregation chamber and defines an upper portion of the disaggregation chamber, the upper member defines an intake channel and an exit channel. The intake channel is fluidically coupled to the disaggregation chamber via an intake opening, and the exit channel is fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the upper member. The exit opening is along the center axis. The upper member includes a protrusion extending from the surface, the protrusion in contact with the raised surface to maintain a distance between the raised surface and the exit opening.

In some embodiments, an apparatus includes an upper portion and a lower portion that collectively define a disaggregation chamber. At least one of the upper or lower portion can include flow structures, such as vanes, ramps, or protrusions that produce a flow pattern to repeatably disaggregate a dry powder by controlling powder release timing and swirl time duration of the dry powder stored within the disaggregation chamber.

In some embodiments, an apparatus includes a lower member and an upper member coupled to the lower member. The lower member defines at least a lower portion of a disaggregation chamber containing a dry powder. The lower member includes a raised surface along a center axis of the disaggregation chamber. The upper member includes a surface that encloses the disaggregation chamber and defines an upper portion of the disaggregation chamber, the upper member defines an intake channel and an exit channel. The intake channel is fluidically coupled to the disaggregation chamber via an intake opening, and the exit channel is fluidically coupled to the disaggregation chamber via an exit opening defined by the surface of the upper member. The lower member and the upper member are collectively configured to deliver a dose of the dry powder independent of an orientation of the lower member and the upper member. For example, in some embodiments, the exit opening is opposite from the raised surface, thus the dose of dry powder is delivered via an annular opening between the raised surface of the lower member and the surface of the upper member. The annular opening (or gap) can prevent powder from remaining on the surface of the upper member if the apparatus is turned upside down. The intake channel also limits the likelihood that the powder will exit (or be spilled) backwards out of the dose chamber by including a series of bends (or a tortuous path).

In some embodiments, a method includes delivering a dose of dry powder from a unit-dose dry powder drug product during patient inspiration. The method includes removing a safety tab and placing an exit opening within a mouth. An airflow is then produced by inspiration, the inspiration occurring for an inspiration time period during which between about 2 liters and 4 liters of air are drawn through the device. In some embodiments, the inspiration time period is at least about four seconds. In response to the airflow, the dry powder is disaggregated within a chamber and delivered via the exit opening. In some embodiments, the dry powder is disaggregated within the chamber for a disaggregation time period of at least about two seconds.

In some embodiments, a method includes moving a strip from a first position between a first member of a dry powder inhaler and a second member of the dry powder inhaler to a second position. The strip seals a dry powder within a portion of a disaggregation chamber defined by a chamber wall of the first member when the strip is in the first position. The portion of the disaggregation chamber is in fluid communication with an exit channel defined by the second member and an intake channel defined by the second member when the strip is in the second position. A mouthpiece of the dry powder inhaler is placed into a mouth. The method further includes inhaling into the mouth to draw an inlet airflow through the intake channel and into the disaggregation chamber. A portion of the intake channel is tangential to a portion of the chamber wall of the first member such that a portion of an inlet airflow has a rotational motion within the disaggregation chamber. The portion of the intake channel can be tangential in one plane (e.g., a top view) and non-tangential in other planes (e.g., a side view). The rotational motion disaggregates the dry powder to produce a plurality of respirable particles within the inlet airflow. The intake channel and the exit channel collectively configured to produce an exit airflow containing the plurality of respirable particles for at least two seconds.

In some embodiments, a kit includes a package containing a dry powder inhaler and an applicator. The dry powder inhaler is configured to deliver a single dose of a dry powder medicament. The applicator is configured to be removably coupled to the dry powder inhaler and allows a caregiver to position the dry powder inhaler for a user without touching the patient or the dry powder inhaler. In this manner, the applicator facilitates maintaining sterility during drug delivery, as well as protecting the caregiver (or administrator) from contamination.

Methods of assembling a medical device are described herein. In some embodiments, a method includes conveying a dry powder into a portion of a disaggregation chamber defined by a first member of a medical device. A strip is coupled to an inner surface of the first member to seal the dry powder within the portion of the disaggregation chamber. A second member of the medical device is placed in contact with the first member such that an inner surface of the second member covers the portion of the disaggregation chamber. The second member defines an intake channel and an exit channel. The exit channel is configured to be fluidically coupled to the disaggregation chamber via an exit opening defined by the inner surface of the second member. The intake channel configured to be fluidically coupled to the disaggregation chamber via an intake port. A flange extending from the inner surface of the first member is deformed to be matingly coupled to a joint surface of the second member to form a sealed joint between the first member and the second member.

In some embodiments, the flange is deformed by heat staking or heat swaging the flange to bend the flange against the joint surface. Such methods of assembly can limit potential adverse effects on the powder that may results from high temperatures or other methods of joining (e.g., ultrasonic welding, radio frequency welding, or the like). Such methods are also easy to implement, thereby reducing the cost and complexity of producing the medical device. Heat-swaging the flange can produce a more air-tight (or hermetic) seal than certain other joining methods, such as press fits, etc.

In some embodiments, the first member and the second member are monolithically constructed from a degradable material, such as, for example, a degradable material that is biodegradable, degradable via exposure to ultraviolet radiation, or degradable, fragmentable, compostable via exposure to any combination of ultraviolet light radiation, oxygen, moisture and biological organisms.

In some embodiments, any of the devices, dry powder inhalers, or methods can contain a dry powder that includes a bronchodilator, such as any of albuterol sulfate, levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, or fenoterol.

As used herein, the words “proximal” and “distal” refer to direction closer to and away from, respectively, a location of administration to a patient. Thus, for example, the end of the medicament delivery device contacting the patient's body for delivery (e.g., the mouth) would be the distal end of the medicament delivery device, while the end opposite the distal end would be the proximal end of the medicament delivery device. It is contemplated that any of the devices described herein can be administered or actuated by either the patient themselves (i.e., self-administration) or a caregiver (e.g., an operator, medical professional, or other administrator).

As used herein, spatially relative terms—such as “beneath”, “below”, “lower”, “above”, “upper”, “proximal”, “distal”, and the like—may be used to describe the relationship of one element or feature to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions (i.e., translational placements) and orientations (i.e., rotational placements) of a device in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be “above” or “over” the other elements or features. Thus, the term “below” can encompass both positions and orientations of above and below. A device may be otherwise oriented (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

The term “about” when used in connection with a referenced numeric indication means the referenced numeric indication plus or minus up to 10 percent of that referenced numeric indication. For example, “about 100” means from 90 to 110.

The term “substantially” when used in connection with, for example, a geometric relationship, a numerical value, and/or a range is intended to convey that the geometric relationship (or the structures described thereby), the number, and/or the range so defined is nominally the recited geometric relationship, number, and/or range. For example, two structures described herein as being “substantially parallel” is intended to convey that, although a parallel geometric relationship is desirable, some non-parallelism can occur in a “substantially parallel” arrangement. By way of another example, a structure defining a mass that is “substantially 90 micrograms (mcg)” is intended to convey that, while the recited volume is desirable, some tolerances can occur when the volume is “substantially” the recited mass (e.g., 90 mcg). Such tolerances can result from manufacturing tolerances, measurement tolerances, and/or other practical considerations (such as, for example, minute imperfections, age of a structure so defined, a pressure or a force exerted within a system, and/or the like). As described above, a suitable tolerance can be, for example, of ±10% of the stated geometric construction, numerical value, and/or range. Furthermore, although a numerical value modified by the term “substantially” can allow for and/or otherwise encompass a tolerance of the stated numerical value, it is not intended to exclude the exact numerical value stated.

As used herein, the term “set” can refer to multiple features or a singular feature with multiple parts. For example, when referring to set of walls, the set of walls can be considered as one wall with multiple portions, or the set of walls can be considered as multiple, distinct walls. Thus, a monolithically-constructed item can include a set of walls. Such a set of walls can include, for example, multiple portions that are either continuous or discontinuous from each other. A set of walls can also be fabricated from multiple items that are produced separately and are later joined together (e.g., via a weld, an adhesive, or any suitable method).

The term “fluid-tight” is understood to encompass hermetic sealing (i.e., a seal that is gas-impervious) as well as a seal that is only liquid-impervious. The term “substantially” when used in connection with “fluid-tight,” “gas-impervious,” and/or “liquid-impervious” is intended to convey that, while total fluid imperviousness is desirable, some minimal leakage due to manufacturing tolerances, or other practical considerations (such as, for example, the pressure applied to the seal and/or within the fluid), can occur even in a “substantially fluid-tight” seal. Thus, a “substantially fluid-tight” seal includes a seal that prevents the passage of a fluid (including gases, liquids and/or slurries) therethrough when the seal is maintained at pressures of less than about 10 kPa. Any residual fluid layer that may be present on a portion of a wall of a container after component defining a “substantially-fluid tight” seal are moved past the portion of the wall are not considered as leakage.

In some embodiments, a drug product configured for administration by an untrained or partially-trained user (such as self-administration by a user) can include any of the medicament compositions described herein. Such drug products can include, for example, a dry powder delivery device configured to provide repeatable (e.g., device-to-device) and accurate dose delivery. One example of such a medicament delivery device is provided inFIGS. 1-3, which are schematic illustrations of a medicament delivery device (or drug product)600according to an embodiment. The medicament delivery device600includes a first member (or portion)620and a second member (or portion)650coupled to the first member620. The first member620defines at least a portion of a disaggregation chamber625(also referred to as a dose chamber) that contains a dry powder P. More particularly, the first member620includes a chamber wall630(shown as a dashed line inFIGS. 1 and 2) that forms an outer boundary of the disaggregation chamber625. The chamber wall630is curved and defines a center axis CA. As described below, in use, a portion of an inlet air flow can flow in a rotational (or swirling manner) within the chamber625, bounded by the chamber wall630, as shown by the arrow A1. The chamber625can be configured such that, as the dry powder P is disaggregated into particles (shown inFIG. 2) within the desired size range, the particles are entrained in the airflow and exit the chamber625via an exit opening656that is defined by the second member650. Although the chamber wall630is shown as being circular, in other embodiments, the chamber wall630(and any of the chambers described herein) can have any suitable shape. For example, in some embodiments, the chamber wall630can be oval, elliptical, polygonal, or spiral shaped.

The second member650includes an inner surface651(seeFIG. 3) that covers the disaggregation chamber625. The inner surface651can be coupled to a corresponding inner surface of the first member620by any suitable mechanism described herein. The slight gap shown inFIG. 3between the first member620and the second member650is only for purposes of illustration to more clearly identify the inner surface651. In reality, the first member620is coupled to the second member650in a manner that prevents air leakage from the interface between the first member620and the second member650. The second member650defines an intake channel660and an exit channel674. The exit channel674is configured to be fluidically coupled to the disaggregation chamber625via an exit opening656defined by the surface651of the second member650. In this manner, when a user inhales on the exit channel674, inlet air can be drawn from the disaggregation chamber625through the exit opening656and into the exit passageway674to deliver a dose of the dry powder P to the user.

As viewed from the top (FIGS. 1 and 2), the intake channel660defines a center line CL that is tangential to a portion of the chamber wall630of the first member620such that a first portion of an inlet airflow (shown as arrow A3inFIG. 3) conveyed into the disaggregation chamber625via the intake channel660initiates a rotational flow A1and particle motion about the center axis CA of the disaggregation chamber625. Similarly stated, at least a portion of the intake channel660is shaped and positioned with respect to the disaggregation chamber625such that the linear momentum of the first portion of the inlet airflow within the intake channel660is transformed into an angular momentum within the disaggregation chamber625(about the center axis CA). In this manner, the intake channel660produces a rotational (or swirling) airflow with disruption at air inlet location(s)within the disaggregation chamber625. In some embodiments, the center line CL can be tangential in one plane (e.g., a top view,FIG. 1) and non-tangential in other planes (e.g., a side view,FIG. 3). In other embodiments, the center line CL need not be tangential to a portion of the chamber wall630.

The intake channel660is configured to be fluidically coupled to the disaggregation chamber625via an intake port665. As described herein, the characteristics of the inlet air flow as it enters the disaggregation chamber625can impact the accuracy and repeatability with which the dry powder P is disaggregated, broken up, and/or otherwise prepared for delivery to the user. For example, in addition to the dose chamber625shape and dimensions (e.g. depth and diameter), the shape and size of the inlet passageways can influence the airflow pattern within the chamber625(see, e.g., the arrow A1inFIG. 2). Referring toFIG. 3, the intake port665is defined at least in part by an intake ramp667that includes a transition surface668. The transition surface668intersects the inner surface651to form an edge or interrupted edge of the second member650. As shown inFIG. 3, the transition surface668forms an exit angle Θ with respect to the surface651. The exit angle Θ can impact the dose release timing by controlling the number of revolutions that entrained particles make within the chamber625before exiting, the efficiency of disaggregation, the percentage of the dose emitted, and the like. Thus, the intake port665and the transition surface668are configured to produce the desired inlet airflow into the disaggregation chamber625such that the desired exit characteristics (e.g., dose release timing, particle size distribution, percentage of dose emitted) are achieved. For example, in some embodiments, the drug product600(or any other drug products described herein) can produce a particle size distribution well suited for reaching the deeper areas (e.g., alveoli) of the lungs.

In some embodiments, the exit angle Θ is less than 105 degrees. Similarly stated, the transition surface668is angled such that a second portion of the inlet airflow A2enters the disaggregation chamber at a flow angle of at least about 75 degrees (measured along the center line CL of the intake channel660). In some embodiments, the transition surface is parallel to the center axis CA of the disaggregation chamber625(i.e., the exit angle Θ is about 90 degrees). By having an exit angle Θ of less 105 degrees (or at about 90 degrees), the transition surface668advantageously produces a sudden expansion into the disaggregation chamber625(as opposed to a more gradual diffusion into the disaggregation chamber625). This arrangement produces disruption of rotational air flow A1when a portion of intake flow A2is conveyed from the intake channel660to the disaggregation chamber625. In some embodiments, the intake air flow generated by the intake channel660and transition to the disaggregation chamber625can produce a rotational flow component A3inFIG. 3as well as a disruptive flow component as indicated by A2inFIG. 3, or can otherwise cause the second portion A2of the inlet airflow to disrupt rotational flow A1(shown inFIG. 2) and “fan out” the rotational air-particle stream in one or more directions that are not tangential to the chamber wall630. This non-tangential flow direction is shown by the arrows A2inFIG. 2, and is similar to the flow structure and concepts described within reference to the device100shown inFIG. 29. This arrangement of disrupted rotational flow enables particles to more easily flow to the exit opening656of the disaggregation chamber625, reduces dose release timing, and provides a higher emitted dose percentage. In some embodiments, the edge between the transition surface668and the inner surface651can be a substantially sharp edge (e.g., have an edge radius of less than about 130 microns (0.005 inches)). This can further enhance flow separation or “fan out” of the second portion of the inlet airflow A2as air is conveyed through the intake port665and into the disaggregation chamber. In other embodiments, however, the edge between the transition surface668and the inner surface651can be curved or have a radius of greater than about 130 microns (i.e., can include an edge break).

The dry powder P included in the medicament delivery device600(or any of the devices described herein) can include any suitable medicament, nutraceutical, or composition. In some embodiments, any of the medicament delivery devices (or drug products) described herein can include a composition including any suitable active pharmaceutical ingredient (API), any suitable excipient, bulking agent, carrier particle, or the like.

In some embodiments, the API can include albuterol sulfate (also referred to as “sulphate,” for example, in Europe). In other embodiments, any of the drug products described herein can include any other bronchodilator. For example, in some embodiments the API can include a short-acting bronchodilator, such as, for example, levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, and/or fenoterol. For example, in some embodiments the API can include a long-acting bronchodilator, such as, for example, aclidinium (Tudorza), arformoterol (Brovana), formoterol (Foradil, Perforomist), glycopyrrolate (SeebriNeohaler), indacaterol (Arcapta), olodaterol (Striverdi Respimat), salmeterol (Serevent), tiotropium bromide (Spiriva), umeclidinium (IncruseEllipta), mometasone furoate powder, flunisolide, budesonide, and/or vilanterol.

As described herein, the dry powder P can also include any suitable excipient, such as, for example, lactose. The dry powder P can often include predominantly the excipient with a small percentage of the mass being the API (e.g., one to ten percent). Thus, the delivery characteristics of the device600can be highly dependent on the lactose characteristics (or the grade of lactose included within the dry powder P). For example, some dry powder P can include a non-sieved lactose with a mean diameter of 60 microns. Such powder formulations therefore include the fine lactose particles (e.g., 1-5 microns), and thus can be more “sticky” than those formulations that do not include as much of the fine particles. The advantage of using such non-sieved lactose is that a higher percentage of fine particles can be delivered, which can be beneficial for the desired treatment (e.g., deep lung delivery or the like). Such non-sieved formulations, however, can require more turbulent airflow to disaggregate the stickier fine particles than is needed for a sieved formulation. Thus, the transition surface668and the exit angle Θ can be optimized for use with (and can provide the desired amount of disruptive airflow) for a non-sieved formulation. Thus, in some embodiments, the dry powder P can include a non-sieved lactose formulation having a mean particle diameter of 60 microns. In other embodiments, the dry powder P can include a sieved lactose formulation having an initial mean particle diameter of 60 microns, but with a substantial amount of the fine particles removed by the sieve operation.

In some embodiments, the medicament delivery device600can include a strip or seal (not shown) that fluidically isolates the portion of the disaggregation chamber625from the intake channel660and/or the exit channel674. In this manner, the disaggregation chamber625functions as a chamber (or a portion of a chamber) within which the dry powder can be both stored and later disaggregated. The strip (or seal) can be any suitable seal shown and described herein (e.g., the strip110of the device100shown below), or can be similar to the partition95shown and described in U.S. Pat. No. 9,446,209 (filed Mar. 7, 2014), entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety. For example, in some embodiments, a strip can be coupled between the first member620and the second member650(e.g., in contact with the inner surface651) to seal and/or maintain the dry powder P within the chamber625. Any such seal member can be formulated to be compatible with any of the medicaments and/or drug compositions disposed within the chamber625. Similarly stated, the seal member can be formulated to minimize any reduction in the efficacy of the drug compositions that may result from contact (either direct or indirect) between the seal member and the drug composition within the chamber625. For example, in some embodiments, the seal member can be formulated to minimize any leaching or out-gassing of compositions that may have an undesired effect on the drug composition within the device600. In other embodiments, the seal member can be formulated to maintain its chemical stability, flexibility, strength, and/or sealing properties when in contact (either direct or indirect) with the drug composition within the device600over a long period of time (e.g., for up to six months, one year, two years, five years, or longer).

In use, the user first removes any packaging or overwrap (not shown inFIGS. 1-3, see the overwrap711described below) from about the device600. The user can then optionally remove any seal from between the first member620and the second member650. The user then places a portion of the device (e.g., a mouthpiece) into or against their mouth. The user then inhales, which draws air through the intake channel660and into the disaggregation chamber625. As described above, the inlet airflow is drawn through the inlet port665, which imparts the desired flow characteristics to the inlet airflow as it enters the chamber625. The inlet airflow moves within the chamber625(see, e.g., the arrows A1and A2inFIG. 2) and entrains the dry powder P stored therein. Continued dynamic motion of the inlet airflow causes disaggregation of the particles, thus producing the desired drug delivery performance characteristics (e.g., emitted dose, fine particle mass) for delivery to the patient via the exit channel674.

The medicament delivery device600(and any of the medicament delivery devices described herein) can be constructed from any suitable materials and can be assembled according to any of the methods described herein. For example, in some embodiments, the first member620and the second member650are monolithically constructed from a polymeric material. In some embodiments, the material can be a degradable material, such as, for example, a degradable material that is biodegradable, degradable via exposure to ultraviolet radiation, or degradable, fragmentable, compostable via exposure to any combination of ultraviolet light radiation, oxygen, moisture and biological organisms.

Although the intake ramp667of the intake port665described above is shown as having a curved surface in one plane, in other embodiments, a medicament delivery device can include an intake port having any suitable curved structure to facilitate production of the desired flow. Similarly stated, although the intake ramp667is shown as being rectangular shaped when viewed in a first plane normal to the center axis CA (e.g., the top view ofFIGS. 1 and 2) and curved in a second plane parallel to the center axis CA (e.g., the side view ofFIG. 3), in other embodiments, an intake port can include curved surfaces in any plane (or planes). For example,FIGS. 4-7are schematic illustrations of a medicament delivery device (or drug product)700according to an embodiment. The medicament delivery device700includes a first member (or portion)720and a second member (or portion)750coupled to the first member720. The first member720defines at least a portion of a disaggregation chamber725that contains a dry powder P. More particularly, the first member720includes a chamber wall730(shown as a dashed line inFIGS. 4, 5, and 7) that forms an outer boundary of the disaggregation chamber725. The chamber wall730is curved and defines a center axis CA. As described below, in use, a portion of an inlet air flow can flow in a rotational (or swirling manner) within the chamber725, bounded by the chamber wall730, as shown by the arrow A1. The chamber725can be configured such that, as the dry powder P is disaggregated into particles (identified as particles P1and P2inFIGS. 5 and 7) within the desired size range, the particles are entrained in the airflow and exit the chamber725via an exit opening756that is defined by the second member750. Although the chamber wall730is shown as being circular, in other embodiments, the chamber wall730(and any of the chambers described herein) can have any suitable shape. For example, in some embodiments, the chamber wall730can be oval, elliptical, polygonal, or spiral shaped.

The second member750includes an inner surface751(seeFIG. 6) that covers the disaggregation chamber725. The inner surface751can be coupled to a corresponding inner surface of the first member720by any suitable mechanism described herein. The slight gap shown inFIG. 3between the first member720and the second member750is only for purposes of illustration to more clearly identify the inner surface751. In reality, the first member720is coupled to the second member750in a manner that prevents air leakage from the interface between the first member720and the second member750. The second member750defines an intake channel760and an exit channel774. The exit channel774is configured to be fluidically coupled to the disaggregation chamber725via an exit opening756defined by the surface751of the second member750. In this manner, when a user inhales on the exit channel774, inlet air can be drawn from the disaggregation chamber725through the exit opening756and into the exit passageway774to deliver a dose of the dry powder P, and specifically the fine particles P2, to the user.

The intake channel760defines a center line CL that is tangential to a portion of the chamber wall730of the first member720such that a first portion of an inlet airflow (shown as arrow A1inFIGS. 5 and 7) conveyed into the disaggregation chamber725via the intake channel760has a rotational motion about the center axis CA of the disaggregation chamber725and/or the exit opening756. Similarly stated, at least a portion of the intake channel760is shaped and positioned with respect to the disaggregation chamber725such that the linear momentum of the first portion of the inlet airflow within the intake channel760is transformed into an angular momentum within the disaggregation chamber725(about the center axis CA). In this manner, the intake channel760produces a rotational (or swirling) airflow within the disaggregation chamber725. In some embodiments, the center line CL can be tangential in one plane (e.g., a top view,FIG. 4) and non-tangential in other planes (e.g., a side view,FIG. 6). In other embodiments, the center line CL need not be tangential to a portion of the chamber wall730.

The intake channel760is configured to be fluidically coupled to the disaggregation chamber725via an intake port765. As described herein, the characteristics of the inlet air flow as it enters the disaggregation chamber725can impact the accuracy and repeatability with which the dry powder P is disaggregated, broken up, and/or otherwise prepared for delivery to the user. Referring toFIG. 6, the intake port765is defined at least in part by an intake ramp767that is curved outwardly towards the chamber wall730. This arrangement causes a second portion A2of the inlet airflow to be conveyed outwardly towards the chamber wall730when conveyed from the intake channel760to the chamber725. In this manner, the rotational flow within the disaggregation chamber725is biased towards and deflects off the outside portion of the disaggregation chamber725, toward the exit opening756. Similarly stated, the second portion of the airflow A2can “bounce” off the outer portion of the wall730and be conveyed through the first portion of the airflow A1and toward the exit opening756. Thus, the particles circulating within the first portion A1of the inlet airflow will flow through (and be disrupted by) the second portion A2of the inlet airflow. Similarly stated, the different direction of airflow streams produces reduced dose release time and increased emitted dose percentage.

Additionally, by deflecting and biasing the rotational flow within the disaggregation chamber725toward the exit opening756, the length of time during which a series of particles resides within the disaggregation chamber725is reduced. Similarly stated, deflecting and biasing the rotational flow within the disaggregation chamber725toward the exit opening756causes the effective clearance of large and/or cohesive powder doses from the disaggregation chamber725.

Referring toFIGS. 4 and 6, in some embodiments, the intake ramp767can be curved outwardly towards the chamber wall730in multiple planes. For example, the intake ramp767defines a first radius of curvature R1within a first plane normal to the center axis CA (e.g., the top view ofFIG. 4). The intake ramp767also defines a second radius of curvature R2within a second plane parallel to the center axis CA (e.g., the side view ofFIG. 6).

In some embodiments, the medicament delivery device700can include properties or characteristics of the medicament delivery device600, and vice-versa. For example, in some embodiments, the intake ramp767can include a transition surface similar to the transition surface668shown and described above. For example, in some embodiments, the intake ramp767can include a transition surface that forms an exit angle of less than about 105 degrees. In some embodiments, the intake ramp767can include a transition surface that forms a substantially sharp edge (e.g., have an edge radius of less than about 130 microns) with the inner surface751.

The dry powder P included in the medicament delivery device700(or any of the devices described herein) can include any suitable medicament, nutraceutical, or composition. In some embodiments, any of the medicament delivery devices (or drug products) described herein can include a composition including any suitable active pharmaceutical ingredient (API), any suitable excipient, bulking agent, carrier particle, or the like.

As described herein, the dry powder P can also include any suitable excipient, such as, for example, lactose. The dry powder P can often include predominantly the excipient with a small percentage of the mass being the API (e.g., one to ten percent). Thus, the delivery characteristics of the device700can be dependent on the lactose characteristics (or the grade of lactose included within the dry powder P). For example, some dry powder P can include a non-sieved lactose with a mean diameter of 60 microns. Such powder formulations therefore include the fine lactose particles (e.g., 1-5 microns), and thus can be more “sticky” than those formulations that do not include as much of the fine particles. The advantage of using such non-sieved lactose is that a higher percentage of fine particles can be delivered, which can be beneficial for the desired treatment (e.g., deep lung delivery or the like). Such non-sieved formulations, however, can require more turbulent airflow to disaggregate the stickier fine particles than is needed for a sieved formulation. Thus, the ramp667can be optimized for use with (and can provide the desired amount of disruptive airflow) for a non-sieved formulation. Thus, in some embodiments, the dry powder P can include a non-sieved lactose formulation having a mean particle diameter of 60 microns. In other embodiments, the dry powder P can include a sieved lactose formulation having an initial mean particle diameter of 60 microns, but with a substantial amount of the fine particles removed by the sieve operation.

In some embodiments, the medicament delivery device700can include a strip or seal (not shown) that fluidically isolates the portion of the disaggregation chamber725from the intake channel760and/or the exit channel774. In this manner, the disaggregation chamber725functions as a chamber (or a portion of a chamber) within which the dry powder can be both stored and later disaggregated. The strip (or seal) can be any suitable seal shown and described herein (e.g., the strip110shown below), or can be similar to the partition95shown and described in U.S. Pat. No. 9,446,209 (filed Mar. 7, 2014), entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The medicament delivery device700can be used in a manner similar to that described above for the medicament delivery device600, or any other methods described herein.

In some embodiments, any medicament delivery devices described herein can include features to facilitate administration of a dry powder medicament by an untrained or partially-trained user (such as self-administration by a user). For example, in some embodiments, a medicament delivery device can include features to limit variation in the airflow resistance through the device. In this manner, the accuracy and repeatability of the device, including the flow rates, velocities, amount of the delivered and/or fine particle fraction of the delivered dose can be improved. For example, in some embodiments, a medicament delivery device can include spacers, protrusions, or the like configured to limit inadvertent or undesired deformation in flow channels (e.g., deformation or blocking of flow paths due to the patient gripping the device). In other embodiments, a medicament delivery device can include one or more barrier surfaces that limit the likelihood that an external opening through which air is drawn will become blocked. For example,FIG. 8is a schematic illustration of a medicament delivery device (or drug product)900according to an embodiment. The medicament delivery device900includes a first member (or portion)920and a second member (or portion)950coupled to the first member920. The first member920defines at least a portion of a disaggregation chamber925that contains a dry powder (not shown). More particularly, the first member920includes a chamber wall930that forms a boundary of the disaggregation chamber925. The chamber925can be configured such that, as the dry powder is disaggregated into particles within the desired size range, the particles are entrained in the airflow and exit the chamber925via an exit opening956that is defined by the second member950(see the exit airflow Aout inFIG. 8). Although the chamber wall930is shown as being curved, in other embodiments, the chamber wall930(and any of the chambers described herein) can have any suitable shape. For example, in some embodiments, the chamber wall930can be conical, oval, elliptical, polygonal, or spiral shaped.

The second member950includes an inner surface951and an outer surface952. The inner surface951covers the disaggregation chamber925and can be coupled to a corresponding inner surface of the first member920by any suitable mechanism described herein. The slight gap shown inFIG. 8between the first member920and the second member950is only for purposes of illustration to more clearly identify the inner surface951. In reality, the first member920is coupled to the second member950in a manner that prevents air leakage from the interface between the first member920and the second member950. The second member950defines an intake channel960and an exit channel974. The exit channel974is configured to be fluidically coupled to the disaggregation chamber925via an exit opening956defined by the surface951of the second member950. In this manner, when a user inhales on the exit channel974(e.g., via a mouthpiece953), inlet air can be drawn from the disaggregation chamber925through the exit opening956and into the exit passageway974to deliver a dose of the dry powder, as shown by the airflow Aout.

The intake channel960is configured to be fluidically coupled to the disaggregation chamber925via an intake port965. The intake channel960is fluidically coupled to an external volume outside of the disaggregation chamber925by an external opening963defined by the outer surface952. As described herein, the characteristics of the inlet air flow as it enters the disaggregation chamber925can impact the accuracy and repeatability with which the dry powder P is disaggregated, broken up, and/or otherwise prepared for delivery to the user. Thus, any obstruction of the external opening963can reduce the amount of inlet airflow (shown as Ain), thereby changing the performance of the medicament delivery device900. Accordingly, the outer surface952includes one or more barrier surfaces984that at least partially surround the external opening963. The set of barrier surfaces984is configured to limit obstruction of the external opening963, which can be caused, for example, by the user's fingers during use of the device. In some embodiments, the set of barrier surfaces984is formed from one or more protrusions extending from the outer surface952of the second member950. In some embodiments, the set of barrier surfaces984are non-planar surfaces that at least partially surround the external opening963. In this manner, when a user's finger (or any other object) contacts the barrier surfaces984, passageways for the inlet airflow Ain will be maintained by the non-planar structure of the barrier surfaces984. In some embodiments, the set of barrier surfaces984defines one or more tortuous paths within the outer surface952of the second member950that are in fluid communication with the external opening963. In this manner, as shown by the arrows entering the external opening963, the barriers984provide a series of alternate paths through which the inlet air can be drawn.

In addition to facilitating a consistent airflow through the disaggregation chamber925, the medicament delivery device900also limits the likelihood that the powder within the disaggregation chamber925will be inadvertently conveyed backwards through the intake channel960. Specifically, as shown, the intake channel960includes multiple bends that limit the likelihood that powder inside the disaggregation channel925will be conveyed out of the chamber925via the intake channel960by tipping and/or changing the orientation of the device900during use. Similarly stated, the intake channel960includes a tortuous path to limit movement of the dry powder from the disaggregation chamber925through the intake channel960and the external opening963.

In some embodiments, the medicament delivery device900can include properties or characteristics of the medicament delivery device600or any of the devices described herein, and vice-versa. For example, in some embodiments, the intake port965can be similar to the intake port665or the intake port765described above. For example, in some embodiments, the intake port965can include a transition surface similar to the transition surface668shown and described above.

In some embodiments, the medicament delivery device900can include a strip or seal (not shown) that fluidically isolates the portion of the disaggregation chamber925from the intake channel960and/or the exit channel974. In this manner, the disaggregation chamber925functions as a chamber (or a portion of a chamber) within which the dry powder can be both stored and later disaggregated. The strip (or seal) can be any suitable seal shown and described herein (e.g., the strip110shown below), or can be similar to the partition95shown and described in U.S. Pat. No. 9,446,209 (filed Mar. 9, 2014), entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

In some embodiments, the first member920and the second member950are monolithically constructed from a polymeric material. Moreover, in some embodiments, the barrier surfaces984are monolithically constructed with the second member950, which, in turn, can be monolithically constructed with the first member920. In this manner, the device900can be a one-piece device that has features (e.g., the barrier surfaces984) that protect the external opening963from obstruction. In some embodiments, the device can be constructed from a degradable material, such as, for example, a degradable material that is biodegradable, degradable via exposure to ultraviolet radiation, or degradable, fragmentable, compostable via exposure to any combination of ultraviolet light radiation, oxygen, moisture and biological organisms.

The medicament delivery device900can be used in a manner similar to that described above for the medicament delivery device600, or any other methods described herein.

FIGS. 9-29show various views of a medicament delivery device (or drug product)100according to an embodiment. The medicament delivery device100includes a lower member (or portion)120and an upper member (or portion)150.FIGS. 9-17show the lower member120and the upper member150in a substantially planar configuration to clearly show the features of each member.FIGS. 18-20show the medicament delivery device100being moved from an opened (or planar) configuration to a closed configuration.FIGS. 21-29show the medicament delivery device100with the inner surface151of the upper member150coupled to the corresponding inner surface121of the lower member120to form the assembled medicament delivery device100. As shown inFIGS. 19 and 20, the upper member150can be rotated or “folded” onto the lower member120, as shown by the arrow AA inFIG. 13and BB inFIG. 20, to form the assembled medicament delivery device100. When assembled, the medicament delivery device100can be similar to, and can include certain features of, any of the medicament delivery devices shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The lower member120includes a first (or inner) surface121(seeFIGS. 13 and 28) and a second (or outer) surface122(seeFIGS. 9 and 10). The inner surface121defines a chamber125and one or more injection molding gate recesses149. The chamber125defines a volume or recess within which any suitable medicament is stored. As shown inFIG. 19, a strip110(also referred to as a seal member or partition) is coupled to the inner surface121to seal and/or maintain a medicament within the chamber125. The strip110can be any suitable member that can be removably coupled about the chamber125. For example, in some embodiments, the strip110can have a peelable heat seal coating to allow the strip110to be removed from the inner surface121by being peeled from the device100. The strip110can be formulated to be compatible with any of the medicaments and/or drug compositions disposed within the chamber125. Similarly stated, the strip110can be formulated to minimize any reduction in the efficacy of the drug compositions that may result from contact (either direct or indirect) between the seal member and the drug composition within the chamber125. For example, in some embodiments, the strip110can be formulated to minimize any leaching or out-gassing of compositions that may have an undesired effect on the drug composition within the device100. In other embodiments, the strip110can be formulated to maintain its chemical stability, flexibility, strength, and/or sealing properties when in contact (either direct or indirect) with the drug composition within the device100over a long period of time (e.g., for up to six months, one year, two years, five years, or longer). In some embodiments, the strip110can include a pull tab portion at the distal end. The pull tab portion can be a portion of the strip110that extends beyond the mouthpiece of the device100and provides a region that the user can easily grasp or pull to remove the strip110.

In addition to providing a volume or reservoir within which a medicament can be stored, the chamber125also functions as a chamber (or a portion of a chamber) within which the medicament can be disaggregated or otherwise prepared for delivery to a patient. Specifically, referring toFIG. 13, the inner surface121includes a raised central surface126and defines a central axis (or centerline) CL. Thus, when the upper member150is coupled to the lower member120, the chamber155(defined by the upper member150) and the chamber125(defined by the lower member120) define a circular shaped chamber about the raised central surface126and the centerline CL. Thus, the chamber125forms at least a portion of a disaggregation (and/or dose preparatory) chamber for the device100. Referring toFIG. 28, the inner surface121includes an outer portion (or wall)130and an inner portion (or wall)134, that each form a portion of (or define) the chamber125. As described below, in use an inlet air flow can flow in a rotational (or swirling manner) within the chamber125, bounded by the outer wall130and the inner wall134, as shown by the arrow BB inFIG. 28or the arrows A1inFIG. 29. The chamber125can be configured such that, as the medicament is disaggregated into particles within the desired size range, the particles are entrained in the airflow and exit the chamber125via an exit opening156that is spaced apart from (and above) the raised surface126. The exit flow is shown by the arrow CC inFIG. 28and the arrow A3inFIG. 29.

As shown inFIGS. 12, 19, and 24, the inner surface121defines a recess136that forms a gap with the mating inner surface151of the upper member150. The recess136provides a space within which a portion of the strip110can be bunched or deformed when being removed from between the upper member150and the lower member120. As described below, the recess136along with the walls137limit binding of the strip110or portions of the strip110(e.g., a pull tab) during removal.

The inner surface121also includes two connection flanges144. During assembly, the connection flanges144are deformed to be matingly coupled to a joint surface186of the upper member150to form a sealed joint between the lower member120and the upper member150.

The second (or outer surface)122includes two side edges140, each of which includes a series of ridges or ribs. The side edges140facilitate gripping and manipulation of the device100when in its assembled state. As shown the device100includes a hinge portion138between the lower member120and the upper member150, and about which the upper member150can be rotated about the lower member120(or vice versa) to form the assembled drug product100(seeFIG. 20). The lower member120defines two coupling slots142that receive the coupling protrusions182of the upper member150when the drug product100is in its assembled configuration. More particularly, the coupling protrusions182are configured to be matingly coupled within the coupling slots142to limit movement of the lower member120relative to the upper member150after the device100is in its assembled configuration. In particular, in some embodiments, the device100can be placed in an initial closed configuration after being molded. The coupling protrusions182are configured to be temporarily locked within the coupling slots142to prevent the device100from being opened, unfolded, or otherwise tampered during shipment to a fill/finish operation. By being shipped in an initial (but not permanent) closed configuration, the internal geometry (e.g., the chambers125,155, the inlet passageways, the exit passageways) are protected from debris, contamination, and the like. Shipping in the closed configuration also reduces the need for additional shipping containers or packaging, thus reducing manufacturing costs. Although the lower member120is shown as defining slots142within which the protrusions182are received, in other embodiments, either of the lower member120or the upper member150can define any combination of slots, openings and/or protrusions.

The upper member150includes a first (or inner) surface151(seeFIGS. 13, 14 and 17) and a second (or outer) surface152(seeFIGS. 9 and 10). The upper member150includes an inlet portion153and an exit portion170. Further, the inner surface151defines a chamber155that, along with the chamber125, forms a disaggregation chamber or volume, as described above. The inner surface151defines one or more coupling recesses179for injection molding gate locations186, and includes the coupling protrusion182and the strip (or pull tab) guide walls137, as described above.

The inlet portion153defines a series of inlet passageways (also referred to as intake channels) through which inlet air flows into the disaggregation chamber when the patient inhales through the device100. As described herein, the characteristics of the inlet air flow as it enters the chambers125,155can impact the accuracy and repeatability with which the medicament within the chambers125,155is disaggregated, broken up, and/or otherwise prepared for delivery to the patient. For example, the shape and size of the inlet passageways can influence the airflow pattern within the chamber125(see, e.g., the arrow BB inFIG. 28and the arrow A1inFIG. 29). The angle of entry, in turn, can impact the number of revolutions that entrained particles make within the chamber125before exiting (see, e.g., the arrow CC inFIG. 28and the arrow A3inFIG. 29). Thus, the inlet portion153is configured to produce the desired inlet airflow such that the desired exit characteristics (e.g., velocity, flow rate, particle size distribution) are achieved. For example, in some embodiments, the drug product100(or any other drug products described herein) can produce a particle size distribution well suited for reaching the deeper areas (e.g., alveoli) of the lungs.

In particular, the inlet portion153includes four inlet passageways (also referred to as intake channels): a first inlet passageway160A, a second inlet passageway160B, a third inlet passageway160C, and a fourth inlet passageway160D. Referring toFIG. 14, the first inlet passageway160A includes an external opening163A through which inlet air is drawn from outside of the device100, and intake port165A through which the inlet air is conveyed into the chambers155,125, and a curved portion therebetween. The second inlet passageway160B includes an external opening163B through which inlet air is drawn from outside of the device100, and intake port165B through which the inlet air is conveyed into the chambers155,125, and a curved portion therebetween. The third inlet passageway160C includes an external opening163C through which inlet air is drawn from outside of the device100, and intake port165C through which the inlet air is conveyed into the chambers155,125, and a curved portion therebetween. The fourth inlet passageway160D includes an external opening163D through which inlet air is drawn from outside of the device100, and intake port165D through which the inlet air is conveyed into the chambers155,125, and a curved portion therebetween.

The outer surface152of the upper member150includes a shroud (or ridge)180that surrounds the external openings163A,163B,163C,163D. The shroud180provides a surface that the user can contact when manipulating the device100when in its assembled state. As described above, the side edges140also facilitate gripping and manipulation. The shroud180can be either continuous or can be interrupted about the outer edge of the upper member150. The shroud180also provides a barrier adjacent the external openings that limit the likelihood that the external openings163A,163B,163C,163D will become obstructed by the user's fingers or other materials during use. In addition to the shroud180, as shown inFIGS. 21 and 22, the outer surface152includes a first set of barrier protrusions (or surfaces)184that at least partially surround the external opening163A and the external opening163B. As shown inFIG. 26A, the outer surface152includes a second set of barrier protrusions (or surfaces)186that at least partially surround the external opening163C and the external opening163D. The barrier surfaces184,185are also configured to limit obstruction of the external openings, which can be caused, for example, by the user's fingers during use of the device. In particular, the set of barrier protrusions184include multiple non-planar surfaces that at least partially surround the external openings163A,163B. In this manner, when a user's finger (or any other object) contacts the barrier surfaces184, passageways for the inlet airflow will be maintained by flow around the non-planar structure of the barrier surfaces184.

The intake ports165A,165B,165C,165D are located on the inner surface151such that they open in to (or are in fluid communication with) the chamber125after the removal of strip (or seal)110that is disposed about the chamber125. In this manner, upon inspiration (inhalation) by the patient, air is drawn from outside of the device through the external openings163A,163B,163C,163D, within the various curved portions of each of the inlet passageways, and into the chamber125via the intake ports165A,165B,165C,165D. As described above, the inlet passageways160A,160B,160C,160D can include any suitable geometry or size to produce the desired airflow characteristics within the chamber125. For example, as shown inFIG. 17, the intake port165A can be defined and/or bounded by an intake ramp167A that includes a termination edge (or surface)168A. Similarly,FIGS. 17 and 27shows a side cross-sectional view of a portion of the intake port165B, which is bounded by an intake ramp167B that includes a termination edge (or surface)168B. The transition of the ramps at the termination edge intersect (or forms an edge with) the inner surface151of the second member150. As described above with reference to the device600, the transition edges (or surfaces)168A,168B each forms an exit angle with respect to the surface151that can have any suitable value. For example, the exit angle can be less than 105 degrees. In some embodiments, the transition surface168A is parallel to the center axis CL of the disaggregation chamber125(i.e., the exit angle is about 90 degrees). By having an exit angle of less 105 degrees (or at about 90 degrees), the transition surface168A advantageously produces a sudden expansion into the disaggregation chamber125. Referring toFIG. 29, this arrangement produces a flow separation or disruption of recirculating rotational flow when a second portion A2of the inlet airflow is conveyed from the intake channel160A to the chamber125. In some embodiments, the flow separation can produce recirculation of the second portion A2of the inlet airflow or can otherwise cause the second portion A2of the inlet airflow to be disrupted or “fan out” in one or more directions that are not tangential to the chamber wall, as shown by the arrows A2inFIG. 29. This arrangement produces improved disaggregation of the dry powder and mixing of the particles within the airflow.

Referring toFIG. 27, in some embodiments, the termination edge (the intersection of the termination surface168A and the inner surface151) can be a substantially sharp edge (e.g., have an edge radius of less than about 50 microns). This can further enhance flow separation as the second portion of the inlet airflow is conveyed through the intake port165A and into the disaggregation chamber. In some embodiments, the inclusion of sharp edges that bound the intake port165A (or any of the exit openings described herein) produces a flow separation when the air flow is conveyed from the inlet passageway to the chamber125. This produces a more dispersed or “fanned-out” air jet within the chamber125, which can facilitate mixing. In other embodiments, however, the edge between the transition surface168A and the inner surface151can be curved or have a radius of greater than about 50 microns (i.e., can include an edge break). In other embodiments, the termination edges can be curved, radiused, interrupted (i.e., can include an edge break), or the like.

The exit ramp167A is the side wall that forms the end portion of the inlet passageway160A and the boundary of a portion of the intake port165A. The exit ramp167A is a curved surface (i.e., a continuous, non-linear surface). The curved shape of the exit ramp167A results in a more gradual (or smoother) exit from this portion of the intake port165A. In some embodiments, the exit ramp167A can be curved in multiple dimensions as described herein. Although the termination surface168A and the exit ramp167A are described with respect to the intake port165A, any of the intake ports described herein can include similar structure. Moreover, although the exit ramp167is described as being curved or non-linear, in other embodiments, the exit ramp167can be a linear “ramped” surface and/or can include linear portion.

The exit portion170of the upper member150includes a top surface171and a curved, distal edge183. The curved distal edge183is aligned with (or mates with) the distal edge143of the lower portion120to define the distal end portion (or mouthpiece) of the device100. The exit portion170defines a central exit opening156, an exit passageway174(seeFIG. 15) and two bypass passageways (see e.g., passageway175A inFIG. 16). The curved distal edge183defines the exit opening178through which the inlet air entrained with the medicament particles is conveyed. Specifically, in use air is drawn from the chamber125,155, through the central exit opening156and into the exit passageway174, as shown by the arrow DD inFIG. 15. The airflow, entrained with medicament particles enters into the exit opening156via a substantially cylindrical flow area (or shroud) defined between the inner surface151of the upper member150and the raised surface126of the lower member120. This flow path produces additional dynamic flow patterns that facilitate further disaggregation of the medicament particles.

As described herein, the dry powder P can also include any suitable excipient, such as, for example, lactose. The dry powder P can often include predominantly the excipient with a small percentage of the mass being the API (e.g., one to ten percent). Thus, the delivery characteristics of the device100can be dependent on the lactose characteristics (or the grade of lactose included within the dry powder P). For example, some dry powder P can include a non-sieved lactose with a mean diameter of 60 microns. Such powder formulations therefore include the fine lactose particles (e.g., 1-5 microns), and thus can be more “sticky” than those formulations that do not include as much of the fine particles. The advantage of using such non-sieved lactose is that a higher percentage of fine particles can be delivered, which can be beneficial for the desired treatment (e.g., deep lung delivery or the like). Such non-sieved formulations, however, can require more turbulent airflow to disaggregate the stickier fine particles than is needed for a sieved formulation. Thus, the transition surface168and the exit angle Θ can be optimized for use with (and can provide the desired amount of disruptive airflow) for a non-sieved formulation. Thus, in some embodiments, the dry powder P can include a non-sieved lactose formulation having a mean particle diameter of 60 microns. In other embodiments, the dry powder P can include a sieved lactose formulation having an initial mean particle diameter of 60 microns, but with a substantial amount of the fine particles removed by the sieve operation.

As shown inFIGS. 13, 15, and 26C, the inner surface151of the upper member includes two protrusions157that are positioned adjacent the exit opening156. When the device100is in its assembled configuration, the two protrusions157contact the raised surface126. This arrangement maintains a constant distance between the exit opening156and the raised surface126, thereby producing a consistent flow area during use, as well as a gap within which the strip110can reside without being pinched between the first member120and the second member150. For example, the contact between the protrusions157and the raised surface126prevents deflection of the upper member150, for example, if the user squeezes the device100during use. Such undesirable deflection could, for example, reduce the flow air thereby choking the flow or otherwise decreasing the flow within the chamber125. Similarly stated, in some embodiments, the annular “air gap” defined between the raised surface126and the exit opening156can be an air flow constriction point, which can generate particle collisions (and disaggregation). Maintaining the constant distance during use (and between various users), as described herein, facilitates a consistent air flow resistance during use. This, in turn, improves dose delivery consistency and maintains a consistent air flow resistance level experienced by the patient. Thus, the protrusion157provides for a more consistent, repeatable delivery of the medicament.

The two bypass passageways (see e.g., passageway175A inFIG. 16) provide a flow path through which a portion of the air produced by inspiration flows outside of the chamber125,155(see also the arrow EE inFIG. 16). Specifically, the exit portion170defines the bypass passageway175A that receives bypass air via the bypass inlet176A (seeFIG. 10) and the bypass passageway that receives bypass air via the bypass inlet176B (seeFIG. 10). As shown inFIG. 9, the curved distal edge183defines the bypass openings177A,177B through which the bypass air flows from the bypass passageways and into the user's mouth. The bypass passageways can be sized (or tuned) to manipulate the air flow resistance through the chamber125.

The medicament delivery device100can be used to treat any number of indications, including asthma and chronic obstructive pulmonary disease (COPD). In use, the user first removes any packaging or overwrap (not shown, but which can be similar to the protective overwrap711shown and described below) from about the device100. The user then removes the strip110by pulling the strip as shown by the arrows inFIG. 25. As described above, the inclusion of the recess136and the strip guide walls137allows portions of the strip110to become compressed together (or bunched up) if pulled slightly to one side or the other (i.e., if pulled in a direction that is not parallel to a longitudinal axis of the strip110). This bunching will provide a region of increased strength, thereby allowing the strip110to be successfully removed from the device100without tearing or breaking. Similarly stated, the recess136and strip guide wall137provide a volume that does not pinch, bind, or otherwise promote tearing of the strip110during removal.

After the strip110is removed, the user then places the distal end portion (or mouthpiece) of the assembled device100into their mouth. The user then inhales, which draws air into the two bypass inlet openings176A,176B, and also the four external openings163A,163B,163C,163D. As described above, the portion of the air that is drawn through the four external openings163A,163B,163C,163D (referred to as the inlet airflow) is conveyed into the chamber125,155via the respective inlet air passageways160A,160B,160C,160D. The structure defining the intake ports165A,165B,165C,165D imparts the desired flow characteristics to the inlet airflow as it enters the chamber125,155, as described herein. The inlet airflow moves within the chamber125(see, e.g.,FIGS. 28 and 29) and entrains the dry powder medicament stored therein. Continued dynamic motion of the inlet airflow causes disaggregation of the particles, thus producing the desired emitted dose and fine particle mass and particle size distribution of dose delivery to the patient. The inlet airflow, entrained with the medicament particles, is then conveyed into the exit passageway174via the opening156, as described above.

The chamber125and the chamber155can be of any suitable size to produce the desired airflow and disaggregation properties. For example, although the chamber125is shown as being deeper than the chamber155, in other embodiments, each of the chamber125and the chamber155can have any suitable depth and/or diameter to achieve the desired drug delivery performance. For example, in some embodiments, an upper member (e.g., the upper member150) can include features that are similar to and/or symmetrical with those features of a mating lower member (e.g., the lower member120). For example, in some embodiments an upper member can include a raised surface, similar to the raised surface126, that defines an opening, similar to the opening156. In this manner, the circular shape of the disaggregation chamber can be produced by both the upper member and the lower member. In other embodiments, a ratio between the depth of a chamber defined by an upper member (e.g., chamber155) to the depth of a chamber defined by a lower member (e.g., chamber125) can be at least 0.75, at least 0.9, or at least 1.0. By producing a substantially symmetrical design (e.g., a ratio of about 1.0), the device can produce the desired airflow entrained with medicament particles independently of the orientation of the device. Similarly stated, this arrangement can produce substantially the same drug delivery characteristics whether the device is used with the upper member (e.g., the upper member150) facing upwards or downwards.

The arrangement of the raised surface126and the curved upper chamber155also limits the likelihood that the powder within the disaggregation chamber125,155will be inadvertently conveyed out of the exit opening156without being properly disaggregated if the device100is tipped or turned upside down during use. Specifically, as described, the dose of dry powder is delivered via an annular opening between the raised surface126of the lower member120and the surface of the upper member150. The annular opening (or gap) can prevent powder from remaining on the surface of the upper member150if the device100is turned upside down. The intake channel also limits the likelihood that the powder will exit (or be spilled) backwards out of the dose chamber by including a series of bends (or a tortuous path).

FIG. 30is a flow chart of a method10of using a dry powder inhaler, according to an embodiment. Although the method10is described with reference to the medicament delivery device100, in other embodiments, the method10can be performed using any of the medicament delivery devices described herein. The method includes moving a strip from a first position between a first member of a dry powder inhaler and a second member of the dry powder inhaler to a second position, at12. The strip seals a dry powder within a portion of a disaggregation chamber defined by a chamber wall of the first member when the strip is in the first position. The portion of the disaggregation chamber is in fluid communication with an exit channel defined by the second member and an intake channel defined by the second member when the strip is in the second position. A mouthpiece of the dry powder inhaler is then placed into a mouth, at14.

The method further includes inhaling into the mouth to draw an inlet airflow through the intake channel and into the disaggregation chamber, at16. A portion of the intake channel is shaped and/or positioned such that a portion of an inlet airflow has a rotational motion within the disaggregation chamber. The rotational motion disaggregates the dry powder to produce respirable particles within the rotational airflow. The intake channel and the exit channel are collectively configured to produce an exit airflow containing the respirable particles for at least two seconds.

In some embodiments, the method10optionally includes disposing of the dry powder inhaler, including the first member and the second member, at17. For example, in some embodiments, the dry powder inhaler is a unit dose device, also known as single-use device that is discarded after use. In some embodiments, the first member and the second member of the dry powder inhaler are monolithically constructed from a degradable material, such as, for example, a degradable material that is biodegradable, degradable via exposure to ultraviolet radiation, or degradable, fragmentable, compostable via exposure to any combination of ultraviolet light radiation, oxygen, moisture and biological organisms. Such material can limit possible issues with discarding the single-use device.

The medicament delivery device100(and any of the medicament delivery devices or drug products described herein) can be produced using any suitable method of assembly or manufacturing. For example,FIG. 31is flow chart of a method20of assembling a dry powder inhaler, according to an embodiment. Although the method20is discussed with reference toFIGS. 18-23(and the medicament delivery device100shown therein), in other embodiments the method20can be used to assembly any suitable device (drug product).

The method optionally includes opening a monolithically constructed device having a first member and a second member joined by a living hinge to expose a disaggregation chamber defined by the first member, at21. The method includes conveying a dry powder into a portion of a disaggregation chamber defined by a first member of a medical device, at22. Referring toFIG. 18, the dry powder is conveyed into the disaggregation chamber125when the device is in the opened configuration. The dry powder can be conveyed using any suitable method, such as, for example, drum filling or a dosator. In some embodiments, the dry powder can be conveyed using any of the methods or structure shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety. In some embodiments, the dry powder can be in the form of a compressed plug of material. In such embodiments, the disaggregation chamber (or the first member120) can include a target surface (or space) for placement of the compressed plug during the fill process. In addition to the open space shown within the disaggregation chamber125(seeFIG. 13), alternative examples of target surfaces (or spaces) are shown inFIGS. 47-49below. Such target surfaces can include an indentation, cut-out or other surface treatment to facilitate placing the dry powder in the desired location within the disaggregation chamber.

After the dry powder is in the disaggregation chamber, a strip (e.g., the strip110) is coupled to an inner surface121of the first member120to seal the dry powder within the portion of the disaggregation chamber, at24. The strip can be spot sealed to the inner surface121, as shown inFIG. 19, to produce a seal around the disaggregation chamber125. Referring toFIG. 20, the second member150of the medical device is then placed in contact with the first member120such that an inner surface151of the second member covers the portion of the disaggregation chamber125, at26. As shown, the second member defining an intake channel and an exit channel The exit channel is configured to be fluidically coupled to the disaggregation chamber via an exit opening defined by the inner surface of the second member. The intake channel is configured to be fluidically coupled to the disaggregation chamber via an intake port. As shown inFIG. 19, in some embodiments, the first member120and the second member150are monolithically constructed, and the second member150is placed about the first member120by bending a living hinge138between the first member and the second member.

The method20further includes deforming a flange (e.g., the flanges144) extending from the inner surface of the first member to be matingly coupled to a joint surface (e.g., the joint surface186) of the second member to form a sealed joint between the first member and the second member, at28. In some embodiments, the flange can be deformed by heat swaging or heat staking the flange to bend the flange against the joint surface. Such methods of assembly can limit potential adverse effects on the powder that may results from high temperatures or other methods of joining (e.g., ultrasonic welding, radio frequency welding, or the like). Such methods are also easy to implement, thereby reducing the cost and complexity of producing the medical device. The heat swage joining method is beneficial for reducing air leakage variability at the inhaler joints without using ultrasonic welding which can be detrimental to the powder (high frequency vibration). Other joining methods such as snap fits require air gaps to reliably join given part tolerances, which leads to air leakage variability.

Referring toFIGS. 22 and 23, the heat swage flanges144are part of the lower portion of the inhaler and the mating joint surfaces186are located on the upper portion of the inhaler.FIG. 23is a close up view of the top portion of the inhaler showing the flanges144in the deformed position to form the joint. As shown, in some embodiments, the upper portion150can include a set of triangular crush ribs187designed to block air flow leakage through the gap along the heat swage joint. In this manner, when a user inhales into the mouthpiece, and flow path along the exterior of the inhaler (e.g., caused by the gap along the joint) will be blocked by the crush ribs187. This ensures that the full amount of inspiration is drawing through the mouthpiece, as intended.

Although the drug product100is shown as including a series of inlet passageways (e.g., inlet passageway160A) that include curved exit ramp (e.g., the exit ramp167A) into the chamber125, in other embodiments, any of the devices and/or drug products described herein can have any suitable exit wall structure. For example, although the drug product100is shown as including a series of intake ports (e.g., intake port165A and165B) defined by a ramp that include vertical (or sharp) transition surfaces (e.g., the transition surfaces168A,168B) into the chamber125, in other embodiments, any of the devices and/or drug products described herein can have an exit wall structure that gradually leads (or diffuses) into the chamber (e.g., the chamber125or any similar chambers described herein).

For example,FIGS. 32A, 32B, and 33show a drug product (or medicament delivery device)800, according to an embodiment. The drug product (or medicament delivery device)800is similar in many respects to the medicament delivery device100shown and described herein, and therefore certain portions of the device800are not described in great detail. As shown, the medicament delivery device800defines a series of air inlet passageways, including the air inlet passageway860B. The device includes an intake ramp867B that is a gradual transition into the chamber825. As shown, the intake ramp867B forms an exit angle Θ with respect to the surface851that is greater than 105 degrees. For example, in some embodiments, the exit angle Θ is about 135 degrees. Similarly stated, the intake ramp867B causes the flow to turn about 45 degrees within the intake channel860B. This arrangement produces less disruptive air jet(s) than those produced with the lower exit angle shown and described above with reference to the device100. Thus, the higher exit angle reduces the amount of flow separation, which biases air/drug flow toward center outlet hole of the dose chamber825as flow re-circulates.FIG. 33is a close-up view ofFIG. 32Bwith the critical inlet air flow control surface867highlighted in bold line weight. Smooth transition air inlets can be beneficial for maximizing particle rotation, increasing dose release time and disaggregation of highly flowable powders.

As described herein, the dry powder P can also include any suitable excipient, such as, for example, lactose. The dry powder P can often include predominantly the excipient with a small percentage of the mass being the API (e.g., one to ten percent). Thus, the delivery characteristics of the device600can be highly dependent on the lactose characteristics (or the grade of lactose included within the dry powder P). For example, some dry powder P can include a non-sieved lactose with a mean diameter of 60 microns. Such powder formulations therefore include the fine lactose particles (e.g., 1-5 microns), and thus can be more “sticky” than those formulations that do not include as much of the fine particles. The advantage of using such non-sieved lactose is that a higher percentage of fine particles can be delivered, which can be beneficial for the desired treatment (e.g., deep lung delivery or the like). Such non-sieved formulations, however, can require more turbulent airflow to disaggregate the stickier fine particles than is needed for a sieved formulation. Thus, on some embodiments, however, the dry powder P can include a sieved lactose formulation having an initial mean particle diameter of 60 microns, but with a substantial amount of the fine particles removed by the sieve operation. Such embodiments, therefore, may not require the high amount of disruptive airflow delivered by some of the embodiments described herein. Thus, the higher exit angel (e.g., of greater about 135 degrees) can produce less turbulence and provide a suitable rotational flow for such a sieved formulation.

FIG. 34shows a medicament delivery device800′, according to an embodiment. The drug product (or medicament delivery device)800′ is similar in many respects to the medicament delivery device100or800shown and described herein, and therefore certain portions of the device800′ are not described in great detail. As shown, the medicament delivery device800′ defines an air inlet passageway860B′ that includes a vertical channel (or side wall)868′ into the chamber825′. The side wall868′ includes an abrupt sharp edge at the transition to the dose chamber825′ to disrupt rotational flow and fan-out flow to enable flow of particles to the air/drug exit opening to improve emitted dose percentage.

In some embodiments, any of the medicament delivery device (or drug products) described herein can have a combination of different inlet passageway geometries and/or different outlet geometries. For example, any of the embodiments described herein can have one or more inlet passageways defined by a vertical wall (as shown by the transition surface168A described above), one or more inlet passageways defined by a gradual wall (as shown by the ramp867B described above), and/or one or more inlet passageways defined by a cylindrical sharp wall (as shown by the wall868′). This can allow the device to be tailored for a specific drug. Specifically, dry powder drug formulations can vary greatly in term of particle size, cohesiveness, surface attraction and flowability. To achieve the desired drug delivery performance (emitted dose and fine particle fraction) for a specific dry powder drug formulation, combinations of abrupt inlets such as vertical wall and smooth transition inlets (such as the 135-degree exit angle) may be integrated into the inhaler design. Using a four-inlet configuration as an example,FIGS. 35A-35Cillustrate some of the possible combinations. In some embodiments, an inhaler design may include two or more air inlets with combinations of abrupt and smooth air inlets.

The medicament delivery devices100′,100″ and100′″ shown inFIGS. 35A-35Ccan be similar to the device100described above, but includes different intake ports. In referring toFIGS. 35A-35C, the arrows A1represent the recirculating airflow within the disaggregation chamber, the arrows A2represent straight inlet air produced by a ramp867B, the arrows A3represent the deflected (or fanned out) inlet air produced by a ramp167B, and the arrow Aout represents the flow of air and drug out of the device.FIG. 35Ashows a device100′ including one vertical wall air inlet (identified as a ramp167B) and three smooth transition air inlets (identified as ramps867B) into the chamber125.FIG. 35Bshows a device100″ including two vertical wall air inlets (identified as ramps167B) and two smooth transition air inlets (identified as ramp867B) into the chamber125.FIG. 35Cshows a device100′″ including three vertical wall air inlets (identified as ramps167B) and one smooth transition air inlet into the chamber125(identified as a ramp867B).

Although the inlet portion153is shown as including four inlet passageways160A,160B,160C,160D, in other embodiments, the device100(and any of the devices shown herein) can include any suitable number of inlet passageways. For example, in some embodiments, a device can include two inlet passageways, three inlet passageways, or even more than four inlet passageways. Moreover, although the inlet passageways160A,160B,160C,160D are shown as having a particular flow geometry, in other embodiments, a device can include any suitable flow geometry for any of the inlet passageways. For example, in some embodiments, a portion of an inlet passageway can include any suitable curves, radius, or edge designs to facilitate the desired entrainment, disaggregation, and/or production of the dry powder medicament therein.

For example,FIGS. 36 and 37show a top view and a perspective view, respectively, of a portion of a medicament delivery device (or drug product)200according to an embodiment. The medicament delivery device200includes a lower member (or portion)220and an upper member (or portion)250.FIG. 37shows the lower member220and the upper member250in a substantially planar configuration to clearly show the features of each member. In use, the upper member250is coupled to the lower member220to form the assembled medicament delivery device200. The medicament delivery device200is similar in many respects to the medicament delivery device100shown and described herein, and therefore certain portions of the device200are not described in great detail. For example, like the device100, when assembled, the medicament delivery device200can be similar to, and can include certain features of, any of the medicament delivery devices shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The lower member220is similar to the lower member120, and is therefore not described in great herein. Specifically, the lower member220defines a chamber225within which any suitable medicament is stored. In addition to providing a volume or reservoir within which a medicament can be stored, the chamber225also functions as a chamber (or a portion of a chamber) within which the medicament can be disaggregated or otherwise prepared for delivery to a patient. Specifically, the lower member220includes a raised central surface226, an outer portion (or wall)230, and an inner portion (or wall)234. Together, these structures form a portion of (or define) the chamber225. As described below, in use an inlet air flow can flow in a rotational (or swirling manner) within the chamber225, bounded by the outer wall230and the inner wall234. The chamber225can be configured such that, as the medicament is disaggregated into particles within the desired size range, the particles are entrained in the airflow and exit the chamber225via an exit opening256that is spaced apart from (and above) the raised surface226.

The upper member250includes a first (or inner) surface251and a second (or outer) surface. The inner surface251defines a chamber255that, along with the chamber225, forms a disaggregation chamber or volume, as described above. The upper member250includes an inlet portion253and an exit portion. The exit portion of the medicament delivery device200is similar to the exit portion170of the device100described above, and is therefore not shown or described herein.

The inlet portion253differs from the inlet portion153of the device100described above, in that the inlet portion253includes different shapes and geometries associated with the inlet passages. As described herein, the inlet portion253defines a series of inlet passageways through which inlet air flows into the disaggregation chamber when the patient inhales through the device200. As described herein, the characteristics of the inlet air flow as it enters the chambers225,255can impact the accuracy and repeatability with which the medicament within the chambers225,255is disaggregated, broken up, and/or otherwise prepared for delivery to the patient. For example, the shape and size of the inlet passageways can influence the airflow pattern within the chamber225. The angle of entry, in turn, can impact the number of revolutions that entrained particles make within the chamber225before exiting. Thus, the inlet portion253is configured to produce the desired inlet airflow such that the desired exit characteristics (e.g., velocity, flow rate, particle size distribution) are achieved.

In particular, the inlet portion253includes four inlet passageways: a first inlet passageway260A, a second inlet passageway260B, a third inlet passageway260C, and a fourth inlet passageway260D. Referring toFIG. 36, the first inlet passageway260A includes an external opening263A through which inlet air is drawn from outside of the device200, and intake port265A through which the inlet air is conveyed into the chambers255,225, and a curved portion therebetween. The second inlet passageway260B includes an external opening263B through which inlet air is drawn from outside of the device200, and intake port265B through which the inlet air is conveyed into the chambers255,225, and a curved portion therebetween. The third inlet passageway260C includes an external opening263C through which inlet air is drawn from outside of the device200, and intake port265C through which the inlet air is conveyed into the chambers255,225, and a curved portion therebetween. The fourth inlet passageway260D includes an external opening263D through which inlet air is drawn from outside of the device200, and intake port265D through which the inlet air is conveyed into the chambers255,225, and a curved portion therebetween.

The exit openings265A,265B,265C,265D are located on the inner surface251such that they open in to (or are in fluid communication with) the chamber225after the removal of any partition or seal that is disposed about the chamber225. In this manner, upon inspiration (inhalation) by the patient, air is drawn from outside of the device through the external openings263A,263B,263C,263D, within the various curved portions of each of the inlet passageways, and into the chamber225via the intake ports265A,265B,265C,265D. As described above, the inlet passageways260A,260B,260C,260D can include any suitable geometry or size to produce the desired airflow characteristics within the chamber225. For example, as shown inFIG. 37, the intake port265A can be defined and/or bounded by a termination edge266A and an exit ramp267A. In contrast to the termination edge166A (which is a linear edge), the termination edge266A is a curved edge that intersects the chamber225, and provides structure that directs the inlet air flow when exiting the inlet passageway260A. Specifically, the termination edge266A is formed by the intersection of the inner surface251and the side wall that defines a portion of the inlet passageway260A.

The exit ramp267A is the side wall that forms the end portion of the inlet passageway260A and the boundary of a portion of the intake port265A. The exit ramp267A is a curved surface (i.e., a continuous, non-linear surface) that terminates, like the termination edge266A, in a sharp edge. Unlike the termination edge266A, however, the curved shape of the exit ramp267A results in a more gradual (or smoother) exit from this portion of the intake port265A. Although the termination edge266A and the exit ramp267A are described with respect to the intake port265A, any of the exit openings described herein can include similar structure.

In some embodiments, the curved termination edge266A and/or the curved exit ramp267A can direct the inlet air flow entering the chamber225toward the outer portion (or wall)230. Because the powder circulation is biased more toward the outer wall230of the dose chamber225, the disaggregated particles within the airflow then flow through and around these biased air inlet jets prior to exiting the chamber225via the exit opening256. This arrangement can cause a portion (similar to the second portion A2shown inFIG. 5) of the inlet airflow to be conveyed outwardly towards the chamber wall230. In this manner, the rotational flow within the disaggregation chamber225is biased towards and deflects off the outside portion of the disaggregation chamber225, toward the exit opening256. Similarly stated, the portion of the airflow can “bounce” off the outer portion of the wall230and be conveyed through the primary circulating airflow (similar to the first portion A1shown inFIG. 5) and toward the exit opening726. Thus, the particles circulating within the primary airflow will flow through (and be disrupted by) a portion of the inlet airflow. In this manner, the flow pattern of the inlet air entering the chamber225can affect the delivery of the disaggregated medicament. In some embodiments, for example, this arrangement can be advantageous for the delivery of cohesive powders with poor flowability. Similarly stated, this arrangement can help “speed up drug release to the patient, for example, by forcing the powder medicament to exit the device200in a shorter period of time. For example, if the patient inhales for four seconds, it may be desirable to release the powder over a two second period of time, rather than a 4 second delivery time. Releasing the powder medicament at a faster rate means fast and efficient powder clearance from the dose chamber, and therefore potentially results in higher emitted dose percentage and more consistent dosing (dose-to-dose uniformity). By delivering a consistent dose with adequate particle size distribution, the drug product can be tailored to match marketed drug products. For example, in some embodiments, the drug product200(or any other drug products described herein) can produce a particle size distribution well suited for reaching the deeper areas (e.g., alveoli) of the lungs.

FIG. 38depicts an inhaler200′ with ‘outside radius air inlets’ having different sizes. Specifically, the inhaler includes radiused termination edges266A,266B,266C and266D that are radiused or ramped air inlets of variable size to guide powder more directly to the outlet in a swirl flow pattern.

Although shown as being circular in shape, in other embodiments, the chamber125(or any of the dose or disaggregation chambers described herein) can have any suitable shape and/or can include any suitable flow structures therein to promote the desired preparation of the medicament for delivery via inhalation.

For example,FIGS. 39 and 40are top views of a portion of a medicament delivery device (or drug product)300according to an embodiment.FIG. 39shows the device300in an opened configuration andFIG. 40shows the device in a closed configuration. The medicament delivery device300includes a lower member (or portion)320and an upper member (or portion)350.FIG. 39shows the lower member320and the upper member350in a substantially planar configuration to clearly show the features of each member. In use, however, the upper member350is coupled to the lower member320to form the assembled medicament delivery device300, as shown inFIG. 40. The medicament delivery device300is similar in many respects to the medicament delivery device100and/or the medicament delivery device200shown and described herein, and therefore certain portions of the device300are not described in great detail. For example, like the devices100,200, when assembled, the medicament delivery device300can be similar to, and can include certain features of, any of the medicament delivery devices shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The upper member350is similar to the upper member150shown and described above. Specifically, the upper member350defines a chamber355that, along with the chamber325, forms a disaggregation chamber or volume, as described above. The upper member350includes an inlet portion353that includes four inlet passageways: a first inlet passageway360A, a second inlet passageway360B, a third inlet passageway360C, and a fourth inlet passageway360D. The first inlet passageway360A includes an external opening through which inlet air is drawn from outside of the device300, and an intake port365A through which the inlet air is conveyed into the chambers355,325. The second inlet passageway360B includes an external opening through which inlet air is drawn from outside of the device300, and an intake port365B through which the inlet air is conveyed into the chambers355,325. The third inlet passageway360C includes an external opening through which inlet air is drawn from outside of the device300, and an intake port365C through which the inlet air is conveyed into the chambers355,325. The fourth inlet passageway360D includes an external opening through which inlet air is drawn from outside of the device300, and an intake port365D through which the inlet air is conveyed into the chambers355,325.

The intake ports365A,365B,365C,365D are located such that they open in to (or are in fluid communication with) the chamber325after the removal of any partition or seal that is disposed about the chamber325. The intake ports365A,365B,365C,365D are shown on the lower member320to identify their location when the device300is in the assembled configuration. In this manner, upon inspiration (inhalation) by the patient, air is drawn from outside of the device through the external openings, within the various curved portions of each of the inlet passageways, and into the chamber325via the intake ports365A,365B,365C,365D. As described above, the inlet passageways360A,360B,360C,360D can include any suitable geometry or size to produce the desired airflow characteristics within the chamber325.

The lower member320defines a chamber325within which any suitable medicament is stored. In addition to providing a volume or reservoir within which a medicament can be stored, the chamber325also functions as a chamber (or a portion of a chamber) within which the medicament can be disaggregated or otherwise prepared for delivery to a patient. Specifically, the lower member320includes a raised central surface326, an outer portion (or wall)330, and an inner portion (or wall)334. Together, these structures form a portion of (or define) the chamber325.

The lower member320differs from the lower member120in that the lower member320includes a series of ramps331. Each ramp331is located adjacent to the region at which the inlet air flow is conveyed from the intake ports365A,365B,365C,365D into the chamber325. In this manner, the ramps331can obstruct any “dead zones” or low flow velocity eddy currents within the chamber325, thereby promoting improved mixing, flow properties and more complete dose delivery from the disaggregation chamber. Similarly stated, the ramps331can direct the flow from one intake port (e.g., intake port365A) away from (or out of the path from) an adjacent intake port (e.g., intake port365B) and toward center to assist clearance of particles from the disaggregation chamber (flow to outlet opening).

FIG. 41is a top view of a portion of a medicament delivery device (or drug product)400according to an embodiment. The medicament delivery device400includes a lower member (or portion)420and an upper member (or portion)450.FIG. 41shows the lower member420and the upper member450in a substantially planar configuration to clearly show the features of each member. In use, however, the upper member450is coupled to the lower member420to form the assembled medicament delivery device400. The medicament delivery device400is similar in many respects to the medicament delivery device100and/or the medicament delivery device200shown and described herein, and therefore certain portions of the device400are not described in great detail. For example, like the devices100,200, when assembled, the medicament delivery device400can be similar to, and can include certain features of, any of the medicament delivery devices shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The upper member450is similar to the upper member150shown and described above. Specifically, the upper member450defines a chamber455that, along with the chamber425, forms a disaggregation chamber or volume, as described above. The upper member450includes an inlet portion453that includes four inlet passageways: a first inlet passageway460A, a second inlet passageway460B, a third inlet passageway460C, and a fourth inlet passageway460D. The first inlet passageway460A includes an external opening through which inlet air is drawn from outside of the device400, and intake port465A through which the inlet air is conveyed into the chambers455,425. The second inlet passageway460B includes an external opening through which inlet air is drawn from outside of the device400, and intake port465B through which the inlet air is conveyed into the chambers455,425. The third inlet passageway460C includes an external opening through which inlet air is drawn from outside of the device400, and intake port465C through which the inlet air is conveyed into the chambers455,425. The fourth inlet passageway460D includes an external opening through which inlet air is drawn from outside of the device400, and intake port465D through which the inlet air is conveyed into the chambers455,425.

The intake ports465A,465B,465C,465D are located such that they open in to (or are in fluid communication with) the chamber425after the removal of any partition or seal that is disposed about the chamber425. The intake ports465A,465B,465C,465D are shown on the lower member420to identify their location when the device400is in the assembled configuration. In this manner, upon inspiration (inhalation) by the patient, air is drawn from outside of the device through the external openings, within the various curved portions of each of the inlet passageways, and into the chamber425via the intake ports465A,465B,465C,465D. As described above, the inlet passageways460A,460B,460C,460D can include any suitable geometry or size to produce the desired airflow characteristics within the chamber425.

The lower member420defines a chamber425within which any suitable medicament is stored. In addition to providing a volume or reservoir within which a medicament can be stored, the chamber425also functions as a chamber (or a portion of a chamber) within which the medicament can be disaggregated or otherwise prepared for delivery to a patient. Specifically, the lower member420includes a raised central surface426, an outer portion (or wall)430, and an inner portion (or wall)434. Together, these structures form a portion of (or define) the chamber425.

The lower member420also includes a series of vanes (also referred to as ridges or partitions)431. Each vane431is located adjacent to the region at which the inlet air flow is conveyed from the intake ports465A,465B,465C,465D into the chamber425. In this manner, the vanes431can direct the flow entering the chamber425, thereby promoting improved mixing, flow properties and more complete dose delivery from the disaggregation chamber. Specifically, the vanes431can divide each jet of inlet air into a first portion that is directed towards inner wall434(see the arrow EE) to assist in clearance of particles from the disaggregation chamber (flow to outlet hole) and a second portion that is directed towards outer wall promote disaggregation of particles430(see the arrow FF).

Although the device100is shown as including two protrusions157that contact the raised surface126, in other embodiments, a device can include any suitable type of flow structures, stiffeners or the like in the region surrounding the exit opening and/or the raised surface. For example,FIG. 42is a top view of a portion of a medicament delivery device (or drug product)500according to an embodiment. The medicament delivery device500includes a lower member (or portion)520and an upper member (or portion)550.FIG. 42shows the lower member520and the upper member550in a substantially planar configuration to clearly show the features of each member. In use, however, the upper member550is coupled to the lower member520to form the assembled medicament delivery device500. The medicament delivery device500is similar in many respects to the medicament delivery device100and/or the medicament delivery device200shown and described herein, and therefore certain portions of the device500are not described in great detail. For example, like the devices100,200, when assembled, the medicament delivery device500can be similar to, and can include certain features of, any of the medicament delivery devices shown and described in U.S. Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which is incorporated herein by reference in its entirety.

The upper member550is similar to the upper member150shown and described above. Specifically, the upper member550defines a chamber555that, along with the chamber525, forms a disaggregation chamber or volume, as described above. The upper member550includes an inlet portion that includes four inlet passageways: a first inlet passageway560A, a second inlet passageway560B, a third inlet passageway (not shown), and a fourth inlet passageway560D.

The exit openings of the inlet passageways are located such that they open in to (or are in fluid communication with) the chamber525after the removal of any partition or seal that is disposed about the chamber525. In this manner, upon inspiration (inhalation) by the patient, air is drawn from outside of the device through the external openings, within the various curved portions of each of the inlet passageways, and into the chamber525, as described above.

The lower member520defines a chamber525within which any suitable medicament is stored. In addition to providing a volume or reservoir within which a medicament can be stored, the chamber525also functions as a chamber (or a portion of a chamber) within which the medicament can be disaggregated or otherwise prepared for delivery to a patient. Specifically, the lower member520includes a raised central surface526, an outer portion (or wall)530, and an inner portion (or wall)534. Together, these structures form a portion of (or define) the chamber525.

The lower member520also includes a series of protrusion (also referred to as posts)531(only one of the six protrusions is labeled). The protrusions531are located surrounding the raised central surface526. Specifically,FIG. 43shows a side view showing the protrusions. In this manner, the protrusions531can direct the flow exiting the chamber525, thereby promoting improved mixing and flow properties. Specifically, the protrusions531can control the exit flow rate of the medicament by deflecting outgoing particles, enhance the deflection of the dry powder (to improve disaggregation) and/or produce more rotation or flow eddies (to improve disaggregation).

Although the protrusions531are shown as being on the lower member, in other embodiments, the protrusions can be on either, the lower member, the upper member, or both. For example,FIG. 44shows a device500′ including protrusions531′ on both the lower member and the upper member.

Although shown as having a circular cross-sectional shape, in other embodiments, the protrusions531can have any suitable shape. For example, in some embodiments, the protrusions531can be rectangular, octagonal, or any other suitable polygon shape. For example,FIGS. 45 and 46show a device500″ including protrusions531″ having a teardrop shape with flat powder control surface.FIG. 47shows a device500′″ including protrusions531′″ having a modified teardrop shape to deflect the flow inward in a different manner Moreover, although the raised central surface126is shown as being substantially flat (or planar), in other embodiments, the raised central surface of any embodiments described herein can have any suitable shape. For example, the raised central surface526can be a convex shape, a concave shape, a spherical shape, or the like.

Although the chamber125and the chamber155are each shown and described has having circular cross-sectional shape, in other embodiments, any of the chambers described herein can have any suitable shape. For example,FIGS. 48-50show schematic illustrations of chambers having non-circular cross-sectional shapes with constriction and expansion areas for rotational flow, and outlets located to pick up fine particles. Specifically,FIG. 48shows a chamber625having target locations622andFIG. 49shows a chamber625′ having target locations622′.FIG. 50shows a chamber625″ having a single target location622″. As described above, the target locations are areas of the chamber that can receive a compressed plug of dry powder. The arrows represent various flow patterns that are facilitated by and/or produced within the chambers.

Although the device700and the device200are shown and described as including an intake ramp (e.g., the ramp767and the ramp267A) that include a curved surface, in other embodiments, a device can include an intake ramp that includes multiple curved surfaces. For example,FIG. 51is a schematic illustration of a medicament delivery device (or drug product)700′ according to an embodiment. The medicament delivery device700′ is similar to the medicament delivery device (or drug product)700described above, and is therefore not described in detail herein. Specifically, the device700′ includes an intake channel760′ that is configured to be fluidically coupled to the disaggregation chamber725′ via an intake port765′. The intake port765′ is defined at least in part by an intake ramp767′ that is curved both outwardly towards the chamber wall and inwardly towards the exit opening. This arrangement creates and narrow tipped opening at the inlet/chamber transition to “nozzle” the inlet flow (i.e., to produce a higher velocity in the inlet flow) downward to disrupt the rotational flow and deflect powder P toward the exit opening756′, as shown by the arrows.

Any of the medicament delivery devices (drug products) described herein can be included within any suitable packaging. For example,FIG. 50depicts a packaging assembly that contains an inhaler707therein. The inhaler707can be similar to any of the devices shown and described herein, such as the medicament delivery device100, and includes an activation trip (pull tab)708sealed inside a protective overwrap711for protection from ultraviolet light and moisture. The overwrap711is heat sealed709on all sides and includes a slit710for easy opening. In some embodiments, the overwrap can be injected and sealed with an inert gas to ensure that the powder (e.g., drug, nutraceuticals) contained in the inhaler707is not stored in an environment including oxygen.

In addition to the concept shown inFIG. 50, the activation trip (pull tab)708may be sealed between the layers of the overwrap711as shown inFIG. 51. In this embodiment, the user can tear or peel open the overwrap711at the slit710location, and remove the inhaler707from the overwrap711. Since the activation strip (pull tab)708is sealed to the overwrap, the activation strip (pull tab)708would be removed from the inhaler as the inhaler707as its pulled out of the overwrap711. This packaging design eliminates one user operational step to simplify use and administration.

In some embodiments, a kit includes a package containing a dry powder inhaler and an applicator. The dry powder inhaler is configured to deliver a unit dose of a dry powder medicament. The applicator is configured to be removably coupled to the dry powder inhaler and allows a caregiver to position the dry powder inhaler for a user without touching the patient or the dry powder inhaler. In this manner, the applicator facilitates maintaining sterility during drug delivery. For example, any of the inhalers described herein may be administered to the patient with use of a wand or holder to help prevent cross contamination from the patient to nurse or caregiver. The wand would clamp onto the inhaler at the rear non-patient contact end and after dose delivery a hand grip located trigger release would be activated for ejection from the wand and disposal of the spent single use inhaler.

Compositions

In some embodiments, any of the medicament delivery devices described herein can include any suitable medicament, nutraceutical, or composition. In some embodiments, any of the medicament delivery devices (or drug products) described herein can include a composition including any suitable active pharmaceutical ingredient (API), any suitable excipient, bulking agent, carrier particle, or the like.

In some embodiments, the API can include albuterol sulfate (also referred to as “sulphate,” for example, in Europe). In other embodiments, any of the drug products described herein can include any other bronchodilator. For example, in some embodiments the API can include a short-acting bronchodilator, such as, for example, levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, and/or fenoterol. For example, in some embodiments the API can include a long-acting bronchodilator, such as, for example, aclidinium (Tudorza), arformoterol (Brovana), formoterol (Foradil, Perforomist), glycopyrrolate (SeebriNeohaler), indacaterol (Arcapta), olodaterol (Striverdi Respimat), salmeterol (Serevent), tiotropium bromide (Spiriva), umeclidinium (IncruseEllipta), mometasone furoate powder, flunisolide, budesonide, and/or vilanterol.

In some embodiments, the API included in any of the drug products described herein can include methylxanthines or theophylline.

In some embodiments, the API included in any of the drug products described herein can include a combination drug. Such combination drugs can be, for example, a combination of either of two long-acting bronchodilators or of an inhaled corticosteroid and a long-acting bronchodilator. Suitable combination drugs include glycopyrrolate/formoterol (Bevespi Aerosphere), glycopyrrolate/indacaterol (UtibronNeohaler), tiotropium/olodaterol (StioltoRespimat), umeclidinium/vilanterol (AnoroEllipta), budesonide/formoterol (Symbicort), fluticasone/salmeterol (Advair), fluticasone/vilanterol (BreoEllipta). Although listed as including “double” combinations, in other embodiments, a drug product described herein can include triple (or quadruple) combinations.

In some embodiments, the API included in any of the drug products described herein can include Roflumilast.

In some embodiments, the API included in any of the drug products described herein can include a salt or ester such as sulfate (sulphate), or propionate or bromide.

In some embodiments, the API included in any of the drug products described herein can include any suitable SABA (short acting beta-agonist), LABA (long acting beta-agonist), LAMA (long acting muscarinic agent), SAMA (short acting muscarinic agent), or ICS (inhaled corticosteroid). For example, inhaled corticosteroids can include any of the corticosteroids described herein (e.g., flunisolide), as well as others, including fluticasone, mometasone, ciclesonide, or beclomethasone.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled anti-infective composition. Such compositions can include, for example, ribavirin, tobramycin, zanamivir, pentamidine, gentamicin, cidofovir, or any combination of these.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled antibiotic and/or antiviral composition. Such compositions can include, for example, antibiotics used to treat tularemia, including streptomycin, gentamicin, doxycycline, and ciprofloxacin. Such compositions can include, for example, antibiotics used to treat inhalational anthrax. Considerable progress in finding new drugs and suitable therapy for treatment of anthrax has been achieved, and such compositions can include levofloxacin, daptomycin, gatifloxacin, and dalbavancin. Such compositions can include, for example, antivirals to treat or prevent influenza (i.e. Relenza-zanamivir—5 mg doses), antivirals used to treat adenovirus pneumonia (e.g., brincidofovir), antivirals to treat RSV (e.g., Ribavirin).

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled composition for patients with cystic fibrosis. Such compositions can include, for example, tobramycin, aztreonam, colistin, mannitol, or pulmozyme.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled vaccine. Such vaccines include, for example, influenza vaccines, tuberculosis vaccines, malaria vaccines, or any other vaccine suitable for delivery in an inhaled powder form.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled medicament for treating anaphylaxis, croup, asthma, or the like. Such compositions can include a local anesthetic. Such compositions can include epinephrine.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled proteins and peptides. Such compositions can include, for example, insulin.

In some embodiments, the API included in any of the drug products described herein can include any suitable inhaled medicaments for biodefense (i.e., antidote treatment nerve agents). Such compositions can include, for example, Atropine or Atropine Sulfate, Pralidoxime, a combination of Atropine and Pralidoxime, Diazepam. Such compositions can be included to treat any indication, such as for use as a sedative to treat anxiety, muscle spasms, and seizures.

In some embodiments, the API included in any of the drug products described herein can include loxapine, alprazolam, fentanyl, or zaleplon.

Suitable excipients can include any composition or additive that form, along with the API, the desired formulation for filling, long term storage, delivery to the target location, or the like. Examples of suitable excipients include lactose, magnesium stearate, magnesium stearate-treated lactose carrier particles, trehalose, any sugars for use as cryoprotectants (e.g., mannitol), compositions used as solubility enhancers (e.g., cyclodextrine), and any combination of the above, including double, triple, or any other combination(s).

In some embodiments, the composition included in any of the drug products described herein can include any suitable naturally-occurring composition, such as nicotine, cannabinoids, or the like.

The drug product100(and any of the drug products described herein) can have any suitable size (e.g., length, width and/or depth) and can contain any suitable volume (or dose amount) of the medicament. In this manner, the chamber125(or any chambers described herein) can be configured to provide a desired fill volume and/or weight, and emitted dose (mass). In some embodiments, for example, the volume of the chamber125(or any chamber described herein) can be such that the fill weight of the composition is approximately 10 mg and the delivery amount of the composition is approximately 10 mg (providing an emitted dose percentage of approximately 85 percent). In other embodiments, however, the dose size (or weight) can range from 5 mg to 50 mg.

The fill weight and/or delivered dose (mass) can be adjusted such that any of the drug products described herein can include and/or deliver a suitable dose for patients within any suitable range. For example, in some embodiments, any of the drug products described herein can deliver a dose suitable for a pediatric patient (e.g., weighing less than 30 kg) or an adult patient (weighing 30 kg or more).

Although shown as defining a reservoir or chamber (e.g., the chamber125) within which a medicament is directly disposed, in other embodiments, any of the drug products described herein can include a pre-sealed container that contains the medicament, and that is disposed within the chamber (e.g., the chamber125) during manufacturing. In this manner, the assembly of the upper member and lower member can be completed in one location and the drug fill/finish operation can be performed in a different location.

In some embodiments, all or a portion of any of the drug products described herein can be color-coded for easier identification (e.g., within hospitals, etc.). In some embodiments, for example, a portion of either the upper member (e.g., upper member150) or the lower member (e.g., lower member120), or both, or additional parts, can be colored. The coloring can indicate any number of parameters associated with the drug product, such as, the medicament, the dose (e.g., adult, pediatric, etc.), and/or the expiration date. In other embodiments, the partition (not shown, but described above) can be colored.

In some embodiments, any of the drug products described herein can include a partition (or seal) that maintains the medicament within the chamber (e.g., the chamber125). In some embodiments, the partition can be coupled to the lower member (e.g., the lower member120) via a small spot seal in conjunction with clamping forces produced between the upper member and the lower member. In use, the spot seals can be configured to rupture, break or tear to facilitate removal of the partition from between the upper member and the lower member.

In some embodiments, any of the drug products described herein can be included within an overwrap (or package) when in its assembled state. In this manner, the mouthpiece of the device can be maintained in a sterile environment during storage. In some embodiments, an end portion of a partition is coupled to the overwrap such that removal of the overwrap also removes the partition, thus preparing (or readying) the device for use.

In some embodiments, a kit includes a medicament delivery device and an applicator. The medicament delivery device can be any of the medicament delivery devices (or drug products) described herein, such as the drug product100or the drug product200. The applicator is configured to be removably coupled to drug product. This arrangement allows a caregiver to position the drug product for use by a user without touching the user or the dry powder inhaler. In this manner, the applicator facilitates maintaining sterility during drug delivery. In some embodiments, the applicator can include an actuator, lever, button, or the like to release the drug product for use by the patient. In some embodiments, the applicator can contain all or a portion of the drug product (e.g., the proximal end). In other embodiments, the applicator can be disposed within an opening, notch or recess defined by either the upper member or the lower member of the drug product.

For example, although the raised surface126is shown as being a flat surface, in other embodiments, any of the raised surfaces described herein can have any suitable shape. For example, in some embodiments, any of the raised surfaces described herein can have curved or spherical surface. In some embodiments, any of the raised surfaces described herein can have a conical surface and/or can be raised to terminate in a point, or be polygonal, ramped or irregular in shape. In other embodiments, any of the raised surfaces described herein can include a series of protrusions, posts or extensions that impact the flow around and/or through the area of the surface.

Moreover, in some cases, the patient may mistakenly breathe out and into the inhaler prior to inhalation. In other words, in some cases, the patient may blow in the reverse direction into the inhaler. In such cases the raised surface (or plateau), such as for example, the raised surface126, serves as an air deflection surface to deflect the reverse direction air flow to the four air channels (e.g., the channels160A-D and openings163A-D) while powder resides safely in the bottom of the dose chamber. The plateau126may be flat as shown inFIG. 13or convex, concave, ramped or with polygonal surfaces aimed to direct reverse air flow to the four openings163A-D, for example. This concept may be applied to inhaler embodiments with two or more air inlets.

In some embodiments, the air inlets and outlets into and out of any of the dose chambers described herein (e.g., the dose chamber125) are be designed to disaggregate and deliver all particles of the powder contained therein. In other embodiments, the air inlets and outlets into and out of any of the dose chambers described herein (e.g., the dose chamber125) can be designed to separate particles with the chamber based on size, mass, geometry, with smaller particles exiting through the outlet and predominately larger lactose carrier particles remaining in the dose chamber after dose delivery. Larger lactose carrier particles with greater mass and centrifugal force flow along the outside walls of the chamber, and have sufficient mass and momentum to withstand air inlet flow jets and eddy currents. Thus, such larger particles remain flowing along the outside walls throughout the inhalation event. Once the inhalation event is complete, the larger lactose particles settle in the bottom of the dose chamber. The recirculation of these larger lactose particles and resulting impact forces is important for breaking the attractive bonds (forces) between drug (API) and lactose particles, as well as breaking up agglomerates. In addition, less lactose or excipient is delivered to the patient which may be beneficial for dosing regimens involving frequent dosing and high powder loading in the patient's lungs.

Although various embodiments have been described as having particular features and/or combinations of components, other embodiments are possible having a combination of any features and/or components from any of embodiments where appropriate. For example, any of the devices shown and described herein can include any of the ramps, protrusion, or other flow structures, as described herein. For example, although the medicament delivery device100shown inFIGS. 9-10is not shown as including any flow structures (e.g., the ramps331), in other embodiments, a medicament delivery device similar to the device100can include one or more flow ramps, similar to the ramps331shown and described above.

Any of the medicament containers described herein can contain any of the epinephrine compositions and/or other drug formulations described herein.