Patent Description:
Dry powder inhalers used to dispense powdered medicaments often strive to provide an entire dry powder dose in a single breath. Such dry powder inhalers are often complex in their design and may involve moving parts. In addition, these complex dry powder inhalers are difficult to produce and assemble at high speeds.

Dry powder inhalers that are constructed to provide dry powder particles to the lungs at inhalation (air flow) rates that are within conventional smoking regime inhalation (air flow) rates may be designed with a linear airflow path between the powder receptacle and the outlet. Dry powder inhalers may contain inhalable powder in a capsule that may be pierced to access the powder. However, loose powder may sometimes unintentionally fall out of such inhalers if the inhaler is inverted or otherwise manipulated in a non-upright position.

<CIT> relates to a system composed of an inhaler and a capsule. <CIT> relates to a nasal delivery device for and method of delivering particulate substance to the nasal airway of a subject.

It is desirable to provide a dry powder inhaler that mitigates unintentional powder leakage from the inhaler. It is desirable to provide a dry powder inhaler that mitigates unintentional powder leakage from a dry powder capsule disposed in the inhaler. It is desirable to provide a capsule for an inhaler that is pierced such that dry powder may be inhaled when desired but that reduces the amount of loose powder within the inhaler (outside of the capsule) when the inhaler is not actively being used. It is desirable to provide an inhaler with a simple design that is easy to manufacture and assemble and that provides the benefit of reduced powder leakage.

According to an embodiment of the present disclosure, an inhaler article comprises a body with an upstream end and a downstream end, a capsule receptacle, and an airflow path extending from the capsule receptacle to an opening at the downstream end. The downstream end is the mouthpiece end of the inhaler article. A capsule is disposed inside the capsule receptacle. The capsule comprises a first end and a second end, and a tubular side wall extending between the first and second ends. The capsule comprises only a single aperture. The single aperture extends through the tubular side wall of the capsule. The capsule further comprises an inhalable powder disposed inside the capsule.

Advantageously, providing only a single aperture in the capsule positioned at the side of the capsule (as opposed to one of the ends) reduces unintentional loss of dry powder from the capsule. It has been found that a single aperture at the side of the capsule allows inhalation of the dry powder from inside the capsule at air flow rates that are within conventional smoking regime inhalation (air flow) rates. The capsule allows use of a simple inhaler design while mitigating powder loss from the inhaler. By using this technique to mitigate powder leakage, the powder remains inside the capsule until it is used or inhaled. Mitigating powder leakage by placing the single aperture on the side of the capsule does not require any changes to the inhaler article itself. Placing the single aperture on the side of the capsule does not require any changes to the capsule as it is manufactured. Forming the single aperture on the side of the capsule may be performed by user as the capsule and inhaler is prepared for use.

The capsule may comprise a first end cap at the first end and a second end cap at the second end. Each of the first and second end caps of the capsule may comprise a hemisphere. The first end of the capsule may be oriented toward the upstream end of the body. The second end may be oriented toward the downstream end of the body. In some embodiments, the single aperture extends through the tubular side wall and is disposed closer to the first end than the second end. In some embodiments, the single aperture extends through the tubular side wall and is disposed closer to the upstream end than the downstream end. According to an embodiment, the first and second end caps do not include any apertures.

Advantageously, positioning the aperture closer to the upstream end provides a greater delivery of powder than positioning the aperture closer to the downstream end of the capsule. Surprisingly, it has been found that positioning the aperture on the side, closer to the upstream end provides the same or nearly the same amount of powder delivery per inhalation (puff) as positioning the aperture at the upstream end of the capsule. Advantageously, positioning the single aperture on the side wall mitigates unintentional loss of dry powder from the capsule.

The position of the aperture may be determined from a midpoint of the capsule measured along a longitudinal axis of the capsule. The midpoint may be determined by dividing the capsule side wall length in half. The distance of the aperture from the midpoint may be determined as the actual measured distance, or as a percentage of the length toward one end or the other (for example, "% toward first end") calculated by dividing the distance of the aperture from the midpoint by the half length of the capsule side wall. The single aperture may be positioned <NUM> % to <NUM> % toward the first end. The single aperture may be positioned <NUM> % or more, <NUM> % or more, <NUM> % or more, or <NUM> % or more toward the first end. The actual distance of the aperture from the midpoint may be selected based on the size of the capsule. In some cases, the capsule is a size <NUM>, size <NUM>, size <NUM>, size <NUM>, or size <NUM> capsule, preferably a size <NUM>. The capsule may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The capsule side wall may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The single aperture may be positioned <NUM> or more, <NUM> or more, or <NUM> or more toward the first end of the capsule, measured from the midpoint. The single aperture may be positioned <NUM> or less, <NUM> or less, or <NUM> or less toward the first end of the capsule, measured from the midpoint. The single aperture may be within <NUM>, within <NUM>, within <NUM>, or within <NUM> of the first end as measured from the first end along a longitudinal axis of the capsule. The single aperture may be within <NUM>, within <NUM>, within <NUM>, within <NUM>, or within <NUM> of the first end cap as measured from the upstream end of the sidewall along a longitudinal axis of the capsule.

Preferably, the capsule receptacle has dimensions that cause the capsule to maintain its orientation within the capsule receptacle. For example, the capsule receptacle may have a width that causes the capsule to remain oriented such that the first end of the capsule points toward the upstream end of the body. A suitable width may be selected based on the width and length of the capsule so that the capsule has some room to move (e.g., vibrate or rotate) inside the capsule receptacle but does not have enough room to turn end-over-end. For example, the capsule may have a length and the capsule receptacle may have a width that is less than the length of the capsule. The capsule receptacle width may also be determined based on the width or diameter of the capsule. For example, the capsule receptacle may have a width (diameter) that is <NUM> % to <NUM> % greater than the width (diameter) of the capsule. The diameter of the capsule receptacle may be <NUM> % to <NUM> % greater or from <NUM> % to <NUM> % greater than the diameter of the capsule. The capsule may be a two-part capsule, where one part has a diameter slightly larger than the other so that the two parts can telescopically fit together. The single aperture may be disposed along the side wall of the capsule in an area where the diameter of the capsule receptacle is only up to <NUM> % greater, or only up to <NUM> % greater, than the diameter of the capsule. If the capsule is positioned in the center of the capsule receptacle, there may be less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, or less than <NUM> space between the capsule side wall and the wall of the capsule receptacle. In some cases, the capsule receptacle is sized for a size <NUM> capsule and may have an inner diameter in a range from about <NUM> to about <NUM>, or about <NUM> to about <NUM>. The capsule receptacle may have a length in a range from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>. The capsule receptacle may define a cylindrical or substantially cylindrical space constructed to contain the capsule. The capsule receptacle may have a substantially uniform or uniform diameter along the length of the capsule receptacle.

The single aperture may have a suitable size that allows a desired amount of powder to exit the capsule upon inhalation. For example, the single aperture may have a diameter of <NUM> or greater, <NUM> or greater, or <NUM> or greater. The single aperture may have a diameter of <NUM> or less, <NUM> or less, or <NUM> or less. The single aperture may have a diameter of <NUM> to <NUM>, <NUM> to <NUM>, or about <NUM>. The single aperture may have an area of <NUM><NUM> or greater, <NUM><NUM> or greater, or <NUM><NUM> or greater. The single aperture may have an area of <NUM><NUM> or less, <NUM><NUM> or less, <NUM><NUM> or less, <NUM><NUM> or less, or <NUM><NUM> or less. The single aperture may have an area of <NUM><NUM> to <NUM><NUM> or <NUM><NUM> to <NUM><NUM>.

The inhaler article may be used for the inhalation of any desired dry powder. According to an embodiment, the capsule contains dry powder comprising particles containing one or more pharmaceutically active agents. Examples of pharmaceutically active agents include nicotine, anatabine, antiviral compounds such as acyclovir; anti-inflammatory compounds such as salicylic acid, aceclofenac, or ketoprofen; antidiabetic compounds such as metformin or glipizide; antihypertensive compounds such as oxprenolol; antiemetic compounds such as promethazine; antidepressant compounds such as seproxetine; anticoagulant compounds such as picotamide; bronchodilators such as clenbuterol; or anticancer compounds such as beta-lapachone. The pharmaceutically active agent may include a pharmaceutically acceptable salt of the agent. Suitable salts include, for example, a salt of lactic acid ("lactate"), tartaric acid ("tartrate" or "bitartrate"), aspartic acid ("aspartate"), pyruvic acid ("pyruvate"), citric acid ("citrate"), salicylic acid ("salicylate"), glutamic acid ("glutamate"), gentisic acid ("gentisate"), benzoic acid ("benzoate"), fumaric acid ("fumarate"), hydrochloric acid ("hydrochlorate"), alfa-resorcylic acid ("alfa-resorcylate"), beta-resorcylic acid ("beta-resorcylate"), oxalic acid ("oxalate"), p-anisic acid ("anisate"), glutaric acid ("glutarate"), and the like. In some cases, the capsule contains nicotine powder. For example, the capsule may contain a dry powder comprising nicotine salt. The dry powder may further contain other components, such as sugar or sugar alcohol, amino acid, flavorant, cough suppressant, or other pharmaceutically acceptable ingredients that are suitable for use in inhalable powders. In one embodiment, the capsule contains nicotine powder comprising nicotine particles, where the nicotine particles comprise nicotine salt, sugar or sugar alcohol, and amino acid. The capsule may further comprise flavor particles, cough suppressant particles, or both flavor and cough suppressant particles. Flavor and cough suppressant particles are collectively referred to here as flavor particles. The capsule may contain an inhalable powder comprising particles with MMAD particle size in the range of <NUM> to <NUM>, or <NUM> to <NUM>. In one embodiment, the capsule contains nicotine powder comprising nicotine particles, where the nicotine particles have MMAD particle size in the range of <NUM> to <NUM>, or <NUM> to <NUM>. The capsule may further contain flavor particles having MMAD particle size of <NUM> or greater, <NUM> or greater, or <NUM> or greater. The flavor particles may have MMAD particle size of <NUM> or less, <NUM> or less, or <NUM> or less. The flavor particles may have MMAD particle size of <NUM> to <NUM> or from <NUM> to <NUM>. In some embodiments, the capsule contains nicotine particles having MMAD particle size in the range of <NUM> to <NUM>, or <NUM> to <NUM> and flavor particles having MMAD particle size of <NUM> to <NUM> or from <NUM> to <NUM>.

The capsule may contain a predetermined amount of nicotine particles and optional flavor particles. The capsule may contain enough nicotine particles to provide at least <NUM> inhalations or "puffs," or at least <NUM> inhalations or "puffs," or at least <NUM> inhalations or "puffs. " The capsule may contain enough nicotine particles to provide from <NUM> to <NUM> inhalations or "puffs," or from <NUM> to <NUM> inhalations or "puffs. " Each inhalation or "puff" may deliver from <NUM> to <NUM> of nicotine particles, from <NUM> to <NUM> of nicotine particles, or about <NUM> of nicotine particles, to the lungs of the user.

The nicotine particles may have any useful concentration of nicotine based on the particular formulation employed. The nicotine particles may have at least about <NUM> wt-% nicotine up to about <NUM> wt-% nicotine, or from about <NUM> wt-% to about <NUM> wt-% nicotine, or from about <NUM> wt-% to about <NUM> wt-% nicotine, or from about <NUM> wt-% to about <NUM> wt-% nicotine, or from about <NUM> wt-% to about <NUM> wt-% nicotine.

The capsule may hold or contain <NUM> or more, or <NUM> or more of nicotine particles. The capsule may hold or contain <NUM> or less, <NUM> or less, <NUM> or less, or <NUM> or less of nicotine particles. The capsule may hold or contain from <NUM> to <NUM> or from <NUM> to <NUM> of nicotine particles. When flavor particles are blended or combined with the nicotine particles in the capsule, the flavor particles may be present in an amount that provides the desired flavor to each inhalation or "puff" delivered to the user. The capsule may hold or contain <NUM> or more, or <NUM> or more of dry powder (also referred to as a powder system). The capsule may hold or contain <NUM> or less, <NUM> or less, <NUM> or less, or <NUM> or less of dry powder. The capsule may hold or contain from <NUM> to <NUM>, from <NUM> to <NUM>, or from <NUM> to <NUM> of a dry powder. The nicotine particles may make up <NUM> wt-% or more, <NUM> wt-% or more, or <NUM> wt-% or more of the dry powder.

The dry powder (powder system) may have a mean diameter of <NUM> or less, or in a range from <NUM> to <NUM>, or from <NUM> to <NUM>. The mean diameter refers to the mean diameter per mass as measured by laser diffraction, laser diffusion, or an electronic microscope, preferably by laser diffraction.

The nicotine in the powder system or nicotine particles may be a pharmaceutically acceptable free-base nicotine, or nicotine salt or nicotine salt hydrate. Useful nicotine salts or nicotine salt hydrates include nicotine pyruvate, nicotine citrate, nicotine aspartate, nicotine lactate, nicotine bitartrate, nicotine salicylate, nicotine fumarate, nicotine mono-pyruvate, nicotine glutamate or nicotine hydrochloride, for example. The nicotine particles preferably include an amino acid. Preferably the amino acid may be leucine such as L-leucine. Providing an amino acid, such as L-leucine, with the particles comprising nicotine may reduce adhesion forces of the particles and may reduce attraction between nicotine particles, thus reducing agglomeration of nicotine particles and adherence of the nicotine particles to surfaces. Similarly, adhesion forces to particles comprising flavor may also be reduced. The powder system may be a free-flowing material and possess a stable relative particle size of each powder component even when the nicotine particles and the flavor particles are combined.

The particles comprising flavor may include a compound to reduce adhesion forces or surface energy and resulting agglomeration. The flavor particle may be surface modified with an adhesion reducing compound to form a coated flavor particle. One preferred adhesion reducing compound is magnesium stearate. Providing an adhesion reducing compound such as magnesium stearate with the flavor particle, especially coating the flavor particle, may reduce adhesion forces of the particles comprising flavor and may reduce attraction between flavor particles and thus reduce agglomeration of flavor particles. Agglomeration of flavor particles with nicotine particles may also be reduced. The powder system described herein thus may possess a stable relative particle size of the particles comprising nicotine and the particles comprising flavor even when the nicotine particles and the flavor particles are combined. The powder system preferably may be free flowing.

Conventional formulations for dry powder inhalation contain carrier particles that serve to increase the fluidization of the active particles since the active particles may be too small to be influenced by simple airflow though the inhaler. The powder system may comprise carrier particles. These carrier particles may be a saccharide such as lactose or mannitol and may have a particle size greater than <NUM>. The carrier particles may be utilized to improve dose uniformity by acting as a diluent or bulking agent in a formulation. In some embodiments, the capsule contains a powder system that is carrier-free or substantially free of a saccharide particle such as lactose or mannitol. By carrier-free, it is meant that the powder system does not contain separate carrier particles (e.g., saccharide particles) in addition to the nicotine particles (which may contain sugar or sugar alcohol) and the optional flavor particles. Being carrier-free or substantially free of a saccharide such as lactose or mannitol may allow the nicotine and to be inhaled and delivered to the user's lungs at inhalation or airflow rates that are similar to typical smoking regime inhalation or airflow rates.

The capsule may be made of any suitable material. For example, the capsule may be made of a polymeric material, gelatin, or any other suitable material for making fillable hard capsules. In one embodiment, the capsule is made from polymeric material, preferably hydroxypropyl-methylcellulose ("HPMC"). For example, the capsule may be a size <NUM> HPMC capsule. The capsule may be a size <NUM> HPMC capsule. The capsule may be a size <NUM> HPMC capsule. The capsule may be a size <NUM> HPMC capsule. The capsule may be a size <NUM> gelatin capsule. The capsule may be a size <NUM> gelatin capsule. The capsule may be a size <NUM> gelatin capsule. The capsule may be a size <NUM> gelatin capsule.

The inhaler article of the present disclosure allows powder to be inhaled at inhalation (air flow) rates that are within conventional smoking regime inhalation (air flow) rates. According to an aspect of the present disclosure, the inhaler article comprises an inhaler body with a tubular side wall defining an interior and a longitudinal center axis. The interior forms a receptacle for housing the capsule containing inhalable powder. The inhaler article further comprises a mouthpiece element. The inhaler body and the mouthpiece have a simple design that is easy to manufacture and easy to assemble into an inhaler article. According to an embodiment, the mouthpiece may be simply inserted into a tubular inhaler body. The mouthpiece element extends along the longitudinal center axis from an upstream end to a downstream end. The upstream end of the mouthpiece element is received in the interior of the inhaler body. The mouthpiece element comprises an airflow channel extending through the mouthpiece element. The downstream end of the mouthpiece element may form or be disposed at the mouth end of the inhaler article. The upstream end of the mouthpiece element is inserted into or disposed inside the inhaler body. The upstream end of the mouthpiece element may form a downstream end of the capsule receptacle. The receptacle may extend from the upstream end of the inhaler body to the upstream end of the mouthpiece element. The inhaler body may have a closed upstream end. The upstream end of the inhaler body may be folded closed. For example, the upstream end of the inhaler body may be folded closed by a fan fold. The upstream end of the inhaler body may form the upstream end of the receptacle. The upstream end of the inhaler body may be opened prior to use, for example by an inhaler holder. The inhaler article may be designed to exhibit a desired resistance to draw ("RTD"). The inhaler article may have an RTD ranging from <NUM> to <NUM> mmWG.

The inhaler article comprises a body that defines the capsule receptacle and an airflow path extending from the capsule receptacle to an opening or outlet. The inhaler article body may be constructed of any suitable material. For example, inhaler article body may be constructed of cellulosic material, polymeric material, metal, or a combination thereof. According to an embodiment, the body is constructed of cellulosic material, preferably paper, paper board, or cardboard. In a preferred embodiment, the inhaler article comprises a tubular body made from paper, paper board, or cardboard. The upstream end of the tubular body made of paper, paper board, or cardboard may be folded closed, preferably by a fan fold. The closed end may be opened prior to use of the inhaler.

The inhaler article may further comprise a wrapper wrapped about at least a portion of the inhaler body. The wrapper may also be wrapped about at least a portion of the mouthpiece element. In some embodiments, the wrapper does not cover the entire length of the mouthpiece element such that a portion of the length of the mouthpiece element is left uncovered. The wrapper may be a paper wrapper, such as a cigarette wrapper or tipping paper.

Advantageously, an inhaler article made of cellulosic material is easy and inexpensive to manufacture, and is environmentally friendly and biodegradable.

The capsule may be sealed within the inhaler article prior to consumption. The capsule may be pre-loaded into the inhaler. The inhaler article, with the capsule contained inside the capsule receptacle, may be contained within a sealed or airtight container or bag. The inhaler article may include one or more peelable or removable seal layers to cover the one or more air inlet channels or the air outlet or mouthpiece of the inhaler article.

The inhaler article may be used with a holder. For example, the inhaler article may be configured for use with a holder that is capable of opening the closed upstream end of the inhaler article. The inhaler article may be configured for use with a holder that is capable of piercing a dry powder capsule housed in the receptacle. The inhaler article may be configured for use with a holder that provides an air inlet for the inhaler article. The holder may be constructed to activate the inhaler article by opening the closed end of the inhaler article. The holder may be constructed to activate the inhaler article by piercing the capsule with a piercing element. The holder may be constructed to release the particles contained inside the capsule and to enable the article to deliver the particles to a consumer. A plurality of inhaler articles may be combined with a holder to form a system or kit. A user may active and use one inhaler article and capsule at a time. A single holder may be utilized on <NUM> or more, or <NUM> or more, or <NUM> or more, or <NUM> or more inhaler articles to activate (puncture or pierce) a capsule contained within each inhaler article and to inhale the powder contained inside the capsule.

According to an embodiment, a method of preparing an inhaler article for use comprises using a piercing element to pierce a single aperture into the tubular side wall of the capsule. The capsule comprises a first end and a second end, and a tubular side wall extending between the first and second ends. The capsule may be disposed inside the capsule receptacle of the inhaler article such that the first end points toward the upstream end of the inhaler article. The capsule comprises an inhalable powder disposed inside the capsule. The method comprises forming a single aperture through the side wall of the capsule. The method may comprise forming the single aperture closer to the first end than the second end. The single aperture may be formed <NUM> % or more, <NUM> % or more, <NUM> % or more, or <NUM> % or more toward the first end, measured from a midpoint of the capsule. The actual distance of the aperture from the midpoint may be selected based on the size of the capsule. In some cases, the capsule is a size <NUM>, size <NUM>, size <NUM>, size <NUM>, or size <NUM> capsule, preferably a size <NUM>. The capsule may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The capsule side wall may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The single aperture may be positioned <NUM> or more, <NUM> or more, or <NUM> or more toward the first end of the capsule, measured from the midpoint. The single aperture may be positioned <NUM> or less, <NUM> or less, or <NUM> or less toward the first end of the capsule, measured from the midpoint. The single aperture may be within <NUM>, within <NUM>, within <NUM>, or within <NUM> of the first end as measured along a longitudinal axis of the capsule.

The method may comprise forming a single aperture in the capsule side wall, the single aperture having a diameter of <NUM> or greater, <NUM> or greater, or <NUM> or greater. The single aperture may have a diameter of <NUM> or less, <NUM> or less, or <NUM> or less. The single aperture may have a diameter of <NUM> to <NUM>, <NUM> to <NUM>, or about <NUM>. The single aperture may have an area of <NUM><NUM> or greater, <NUM><NUM> or greater, or <NUM><NUM> or greater. The single aperture may have an area of <NUM><NUM> or less, <NUM><NUM> or less, <NUM><NUM> or less, <NUM><NUM> or less, or <NUM><NUM> or less. The single aperture may have an area of <NUM><NUM> to <NUM><NUM> or <NUM><NUM> to <NUM><NUM>.

The inhaler may be less complex and have a simplified airflow path as compared to conventional dry powder inhalers. The inhaler may be constructed to provide a swirling air flow that causes the capsule to rotate about its longitudinal axis upon inhalation. Advantageously, rotation of the capsule within the inhaler more effectively aerosolizes the dry powder and may assist in maintaining a free-flowing powder. Thus, the inhaler article may not require the elevated inhalation rates typically utilized by conventional inhalers to deliver the nicotine particles described above deep into the lungs.

The inhaler article and the capsule may use a flow rate of <NUM>/min or less, <NUM>/min or less, <NUM>/min or less, or <NUM>/min or less. Preferably, the flow rate may be in a range from <NUM>/min to <NUM>/min or from <NUM>/min to <NUM>/min. Preferably, the inhalation rate or flow rate may be similar to that of Health Canada smoking regime, that is, <NUM>/min.

The inhaler and capsule may be used by a consumer similar to smoking a conventional cigarette or vaping an electronic cigarette. Such smoking or vaping may be characterized by two steps: a first step during which a small volume containing the full amount of nicotine desired by the consumer is drawn into the mouth cavity, followed by a second step during which this small volume comprising the aerosol comprising the desired amount of nicotine is further diluted by fresh air and drawn deeper into the lungs. Both steps are controlled by the consumer. During the first inhalation step the consumer may determine the amount of nicotine to be inhaled. During the second step, the consumer may determine the volume for diluting the first volume to be drawn deeper into the lungs, maximizing the concentration of active agent delivered to the airway epithelial surface. This smoking mechanism is sometimes called "puff-inhale-exhale.

The term "nicotine" refers to nicotine and nicotine derivatives such as free-base nicotine, nicotine salts, and the like.

The term "flavorant" or "flavor" refers to organoleptic compounds, compositions, or materials that alter and are intended to alter the taste or aroma characteristics of nicotine during consumption or inhalation thereof.

The terms "upstream" and "downstream" refer to relative positions of elements of the holder, inhaler article and inhaler systems described in relation to the direction of inhalation air flow as it is drawn through the body of the holder, inhaler article and inhaler systems.

Unless otherwise specified, the term "particle size" as used here refers to mass median aerodynamic diameter (MMAD). MMAD is preferably measured with a cascade impactor.

The term "substantially" as used here has the same meaning as "significantly," and can be understood to modify the term that follows by at least about <NUM> %, at least about <NUM> %, or at least about <NUM> %.

The term "not substantially" as used here has the same meaning as "not significantly," and can be understood to have the inverse meaning of "substantially," i.e., modifying the term that follows by not more than <NUM> %, not more than <NUM> %, not more than <NUM> %, or not more than <NUM> %.

For the purpose of the present description and of the appended claims, except where otherwise indicated, all numbers expressing amounts, quantities, percentages, and so forth, are to be understood as being modified in all instances by the term "about. " Also, all ranges include the maximum and minimum points disclosed and include any intermediate ranges therein, which may or may not be specifically enumerated herein. In this context, therefore, a number A is understood as A ± <NUM> % of A. Within this context, a number A may be considered to include numerical values that are within general standard error for the measurement of the property that the number A modifies. The number A, in some instances as used in the appended claims, may deviate by the percentages enumerated above provided that the amount by which A deviates does not materially affect the basic and novel characteristic(s) of the claimed invention. Also, all ranges include the maximum and minimum points disclosed and include any intermediate ranges therein, which may or may not be specifically enumerated herein.

Terms such as "a," "an," and "the" are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration.

The terms "a," "an," and "the" are used interchangeably with the term "at least one. " The phrases "at least one of" and "comprises at least one of" followed by a list refers to any one of the items in the list and any combination of two or more items in the list.

As used here, the term "or" is generally employed in its usual sense including "and/or" unless the content clearly dictates otherwise.

As used here, "have", "having", "include", "including", "comprise", "comprising" or the like are used in their open-ended sense, and generally mean "including, but not limited to. " It will be understood that "consisting essentially of," "consisting of," and the like are subsumed in "comprising" and the like. As used herein, "consisting essentially of," as it relates to a composition, product, method or the like, means that the components of the composition, product, method or the like are limited to the enumerated components and any other components that do not materially affect the basic and novel characteristic(s) of the composition, product, method or the like.

The words "preferred" and "preferably" refer to embodiments that may afford certain benefits, under certain circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the disclosure, including the claims.

A capsule <NUM> containing inhalable powder <NUM> is shown in <FIG>. The capsule <NUM> comprises a first end <NUM> and a second end <NUM>. The capsule <NUM> may comprise a first end cap <NUM> at the first end <NUM> and a second end cap <NUM> at the second end <NUM>. The capsule <NUM> comprises a tubular side wall <NUM> extending between the first and second ends <NUM>, <NUM>, or between the first and second end caps <NUM>, <NUM>. Each of the first and second end caps <NUM>, <NUM> of the capsule may be shaped as a hemisphere, as shown. The capsule <NUM> comprises only a single aperture <NUM>. The single aperture <NUM> extends through the tubular side wall <NUM> of the capsule <NUM>.

In some embodiments, the single aperture <NUM> is disposed closer to the first end <NUM> than the second end <NUM>. The distance of the aperture <NUM> may be determined from a midpoint <NUM> of the capsule, measured along a longitudinal axis A20 of the capsule <NUM>. The capsule side wall <NUM> has a length <NUM>, and the midpoint <NUM> defines a half length L26. The first and second end caps <NUM>, <NUM> each have a length L23, L24, respectively. The total length L20 of the capsule <NUM> is the side wall length L25 plus the length L23 of the first end cap <NUM> and the length L24 of the second end cap.

The distance D30 of the aperture <NUM> from the midpoint <NUM> may be determined as the actual measured distance, or as a percentage of the length toward one end of the other (for example, "% toward first end") calculated as D30/L26. The single aperture <NUM> may be positioned <NUM> % to <NUM> % toward the first end <NUM>. The single aperture <NUM> may be positioned <NUM> % or more, <NUM> % or more, <NUM> % or more, or <NUM> % or more toward the first end <NUM>. The actual distance D30 of the aperture <NUM> from the midpoint <NUM> may be selected based on the size of the capsule <NUM>. In some cases, the capsule <NUM> is a size <NUM>, size <NUM>, size <NUM>, size <NUM>, or size <NUM> capsule, preferably a size <NUM>. The capsule <NUM> may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The capsule side wall <NUM> may have a length of about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. The single aperture <NUM> may be positioned <NUM> or more, <NUM> or more, or <NUM> or more toward the first end <NUM> of the capsule <NUM>, measured from the midpoint <NUM>. The single aperture <NUM> may be positioned <NUM> or less, <NUM> or less, or <NUM> or less toward the first end <NUM> of the capsule <NUM>, measured from the midpoint <NUM>. The single aperture <NUM> may be within <NUM>, within <NUM>, within <NUM>, or within <NUM> of the first end <NUM> as measured from the first end <NUM> along a longitudinal axis A20 of the capsule <NUM>.

An inhaler article <NUM> containing the capsule <NUM> is shown schematically in <FIG>. The inhaler article <NUM> has a first, downstream end <NUM> and an opposing second, upstream end <NUM>. A mouthpiece element <NUM> is disposed at the downstream end <NUM> of the inhaler article <NUM>. The outside surface of the inhaler article <NUM> may be formed, at least in part, by a wrapper <NUM>. The inhaler article <NUM> comprises an inhaler body <NUM> with a tubular side wall <NUM>. The inhaler body <NUM> defines an interior that forms a receptacle <NUM> for housing the capsule <NUM>. The inhaler body <NUM> further defines a longitudinal center axis A. The mouthpiece element <NUM> extends along the longitudinal center axis A. The mouthpiece element <NUM> may be at least partially inserted into the inhaler body <NUM>. The mouthpiece element <NUM> has a downstream end <NUM> and an upstream end <NUM>. The upstream end <NUM> of the mouthpiece element <NUM> is received in the interior of the inhaler body <NUM> and forms the downstream end of the capsule receptacle <NUM>.

The first end <NUM> of the capsule <NUM> may be oriented toward the upstream end <NUM> of the body. The second end <NUM> may be oriented toward the downstream end <NUM> of the body. In some embodiments, the single aperture <NUM> extends through the tubular side wall <NUM> and is disposed closer to the first end <NUM> of the capsule <NUM> and the upstream end <NUM> of the inhaler article <NUM> than the second end <NUM> and the downstream end <NUM>.

The inhaler article <NUM> may be used with a holder <NUM>, as shown in <FIG>. The holder <NUM> may be configured to open the upstream end <NUM> of the inhaler article <NUM>. The holder <NUM> may be configured to provide an air inlet <NUM> for the inhaler article <NUM>. The holder <NUM> may further be configured to pierce the capsule <NUM>. The holder <NUM> may be configured to make a single aperture <NUM> on the side wall <NUM> of the capsule <NUM>. When a user draws air through the inhaler article to use the inhaler, air may flows from the air inlet <NUM>, through the receptacle <NUM>, entrain dry powder particles from inside the capsule <NUM>, and flow through the mouthpiece element <NUM>, and out the outlet <NUM>. According to an embodiment, a dry powder may be inhaled from the capsule <NUM> at an airflow rate of <NUM>/min or less, or <NUM>/min or less.

The capsule receptacle <NUM> may have width (diameter) W102 that is less than the length L20 of the capsule <NUM> such that the capsule <NUM> maintains its orientation within the capsule receptacle <NUM>. The first end <NUM> of the capsule <NUM> is oriented toward the upstream end <NUM>, and the second end <NUM> of the capsule <NUM> is oriented toward the downstream end <NUM> of the inhaler <NUM>. As shown in <FIG>, the capsule <NUM> may have room to move slightly (e.g., vibrate and rotate) but not enough to turn end over end. The capsule has a width (diameter) W20. The width (diameter) W102 of the capsule receptacle <NUM> may be <NUM> % to <NUM> % greater, <NUM> % to <NUM> % greater, or <NUM> % to <NUM> % greater than the width (diameter) W20 of the capsule <NUM>.

The performance of powder delivery of capsules having a single aperture at different locations was tested. Each of the capsules was a size <NUM> HPMC capsule (having a total length of <NUM> ± <NUM>) and contained <NUM> of powder containing nicotine salt and flavor particles. The apertures were made with a needle having a diameter of <NUM>.

Sample <NUM> was a capsule with a single aperture at the center of the first (upstream) end.

Sample <NUM> was a capsule with a single aperture at the side wall, positioned closer to the first (upstream) end. The aperture of Sample <NUM> was <NUM> from the downstream end, or <NUM> from the upstream end of the capsule.

Sample <NUM> was a capsule with a single aperture at the side wall, positioned closer to the second (downstream) end. The aperture of Sample <NUM> was <NUM> from the downstream end of the capsule.

The samples were tested by placing the capsule in an inhaler article capsule receptacle and drawing air through the inhaler article. The air draw pattern mimicked smoking a cigarette, drawing <NUM> or air for <NUM> sec (a single puff), <NUM> times. The amount of powder delivered over <NUM> puffs was measured. The results are shown in TABLE <NUM> below.

Claim 1:
An inhaler article (<NUM>) comprising:
a body (<NUM>) comprising an upstream end (<NUM>) and a downstream end (<NUM>), a capsule receptacle (<NUM>), and an airflow path extending from the capsule receptacle to an opening at the downstream end; and
a capsule (<NUM>) disposed inside the capsule receptacle, the capsule comprising:
a first end (<NUM>) and a second end (<NUM>);
a tubular side wall (<NUM>) extending between the first and second ends;
only a single aperture (<NUM>) in the capsule, the single aperture extending through the tubular side wall; and
an inhalable powder (<NUM>) disposed inside the capsule,
wherein the first end of the capsule is oriented toward the upstream end of the body, and wherein the single aperture is disposed closer to the first end than the second end.