Abstract:
A novel metering valve having improved flow for delivery of an aerosol formulation is disclosed. Methods of delivering an aerosol formulation using a device comprising the novel metering valve are also disclosed.

Description:
[0001]    This application claims the benefit of U.S. provisional patent application Ser. No. 60/278,890, filed Mar. 26, 2001. 
     
    
     
       BACKGROUND  
         [0002]    Metering valves are a common means by which aerosols are dispensed from aerosol containers. Metering valves are particularly useful for administering medicinal formulations that include a liquefied gas propellant and are delivered to a patient in an aerosol.  
           [0003]    When administering medicinal formulations, a dose of formulation sufficient to produce the desired physiological response is delivered to the patient. The proper, predetermined amount of the formulation must be dispensed to the patient in each successive dose. Thus, any dispensing system must be able to dispense doses of the medicinal formulation accurately and reliably to help assure the safety and efficacy of the treatment.  
           [0004]    Metering valves have been developed to provide control over the dispensing of medicinal aerosol formulations. A metering valve may be used to regulate the volume of a medicinal formulation passing from a container to a metering chamber, which defines the maximum amount of the formulation that will be dispensed as the next dose. The precise dosage metered by the metering chamber may be dependent, in part, upon the physical conditions under which the medicinal formulation is permitted to fill the metering chamber. Reliable and controllable flow of the medicinal formulation into the metering chamber may contribute to the accuracy and/or precision of the metering of successive doses of the formulation. Thus, reliable and controllable flow of the medicinal formulation into the metering chamber may improve performance of the metering valve and, therefore, may be highly desirable.  
           [0005]    In some metering valves, the metering chamber fills with the medicinal formulation prior to the patient actuating the valve stem and thereby releasing the dose. The metering chamber is refilled with formulation after dispensing one dose so that the metering valve is ready to discharge the next dose. Consequently, the metering chamber contains formulation at all times except for the brief time during which the valve stem is depressed by the user to discharge a dose. Also, the passageways through which the formulation must flow to reach the metering chamber are often narrow and tortuous. As a result, metering valves configured in this way have a number of disadvantages resulting in, for example, erratic dosing due to loss of prime, i.e., the occurrence of vapor or air voids in the metered volume, which may leading to a shortfall in the volume of dose being metered by the valve.  
           [0006]    In other metering valves, the metering chamber does not materialize unless and until the valve stem is actuated. Actuation of these valve stems can be divided into a filling stage and a discharge stage. The filling stage begins as the valve stem is depressed during actuation. The action of depressing the valve stem causes the formation of a transient metering chamber. As the valve stem is depressed, the transient metering chamber expands and formulation enters the metering chamber. As displacement of the valve stem continues, a stage is reached at which filling of the transient metering chamber stops. Eventually, displacement of the valve stem continues to the discharge stage, in which the metered formulation is discharged. In these valves, a single actuation thus causes rapid filling of the transient metering chamber followed by discharge of the formulation to the patient. Thus, the metered formulation does not reside for any appreciable amount of time in the metering chamber.  
           [0007]    While a metering valve having a transient metering chamber provides advantages over other types of metering valves for the delivery of aerosol formulations, the flow of formulation from the container to the metering chamber may be disrupted. When this happens, formulation may be delivered in inconsistent or inaccurate doses.  
           [0008]    What is needed is a valve stem for a metered dose inhaler that improves flow of formulation into the metering chamber, thereby providing consistent, accurate, dosages of formulation, even when actuated rapidly.  
         SUMMARY  
         [0009]    It has been determined that one cause of disrupted flow of formulation may be due to the design of the valve stem in the metering valve. A seal typically isolates the metering chamber from the aerosol container once the correct volume of formulation has been metered. To accomplish this, the seal must occlude the flow path, through which formulation must pass in order to fill the metering chamber, as the valve stem is depressed beyond the filling stage. As used herein, occlude refers to at least a partial closing off of an opening by a seal, gasket, or diaphragm. In certain metering valves, the passageways leading from the container to the metering chamber can begin to become occluded well before the formulation has completed filling the metering chamber. This effectively begins to cut off flow of formulation into the metering chamber while the valve stem is still in the filling stage of actuation.  
           [0010]    Also, the design of the valve stem may cause regions of recirculation or localized low pressure to develop in the flow of formulation into the metering chamber. Such low pressure regions can lead to incomplete metering of the formulation by allowing bubbles to form in the metered volume, particularly when the patient actuates the valve rapidly or rapid actuation occurs due to the mechanism of a breath actuated device.  
           [0011]    The present invention provides a valve stem for a metered dose inhaler that improves the flow of formulation into the metering chamber. The novel stem design has a short, but circumferentially widened channel opening that, in many embodiments, enhances the flow of formulation into the metering chamber. Accordingly, the present invention provides an aerosol valve stem including a body that includes a body wall defining an internal chamber; at least one inlet port through the body wall in fluid communication with the internal chamber; a channel opening in the body wall having a height and a width wherein the width is greater than the height; and at least one channel providing fluid communication between the internal chamber and the channel opening.  
           [0012]    In some embodiments, the valve stem may include a plurality of channel openings in the body wall. In these embodiments, the plurality of channel openings may define a cumulative width that is greater than the height of the channel openings.  
           [0013]    In another aspect, the present invention provides a method of delivering an aerosol dose of medicine including providing an inhaler that includes an aerosol valve stem including: a body that includes a body wall defining an internal chamber, at least one inlet port through the body wall in fluid communication with the internal chamber, a channel opening in the body wall having a height and a width wherein the width is greater than the height, at least one channel providing fluid communication between the internal chamber and the channel opening; providing a formulation of aerosol medicine contained within the inhaler; and actuating the inhaler.  
           [0014]    In yet another aspect the present invention provides a metering valve that includes a housing that includes an internal chamber defined by one or more chamber walls, the internal chamber comprising an outlet aperture; a diaphragm positioned at the outlet aperture and in sealing engagement with at least a portion of the housing; a metering gasket in sealing engagement with one or more chamber walls; a valve stem including: i) a body that comprises a body wall defining an internal chamber, ii) at least one inlet port through the body wall in fluid communication with the internal chamber, iii) a channel opening in the body wall having a height and a width wherein the width is greater than the height, and iv) at least one channel providing fluid communication between the internal chamber and the channel opening, wherein the valve stem passes through the aperture in slidable sealing engagement with both of the diaphragm and the metering gasket; and an annular space having a width defined by a distance between the chamber wall and the valve stem.  
           [0015]    In some embodiments, the valve stem may include a plurality of channel openings in the body wall. In these embodiments, the plurality of channel openings may define a cumulative width that is greater than the height of the channel openings. In certain embodiments, the height of at least one channel opening may be from about 1 to about 5 times the width of the annular space. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]    [0016]FIG. 1 is a cross-sectional view of a metered dose inhaler including the aerosol valve of the present invention.  
         [0017]    [0017]FIG. 2 is an enlarged cross-sectional view of the aerosol valve of the present invention in the resting position.  
         [0018]    [0018]FIG. 3 is an enlarged cross-sectional view of the aerosol valve of the present invention during the filling stage of valve stem actuation.  
         [0019]    [0019]FIG. 4 is an enlarged cross-sectional view of the aerosol valve of the present invention in the filled stage of valve stem actuation.  
         [0020]    [0020]FIG. 5 is an enlarged cross-sectional view of the aerosol valve of the present invention during the discharge stage of valve stem actuation.  
         [0021]    [0021]FIG. 6 a  is a side view of an alternative embodiment of the aerosol valve stem of the present invention.  
         [0022]    [0022]FIG. 6 b  is a view of a half section of an alternative embodiment of the aerosol valve stem of the present invention.  
         [0023]    [0023]FIG. 7 is an enlarged cross-section of an alternative embodiment of the aerosol valve stem of the present invention.  
         [0024]    [0024]FIG. 8 is an enlarged cross-section of another alternative embodiment of the aerosol valve stem of the present invention.  
         [0025]    [0025]FIG. 9 is an enlarged cross-section of another alternative embodiment of the aerosol valve stem of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0026]    The following description is set forth in terms of aerosol metering valves used to dispense an aerosol formulation from an aerosol container. However, the metering valves and methods of the present invention have application to the delivery of virtually any pressurized fluid in an accurate, metered dose. In particular, the metering valves described herein are useful for dispensing medicinal aerosol formulations.  
         [0027]    When used to dispense medicinal aerosol formulations, the metering valves of the present invention may be used to administer virtually any aerosol formulation of drug into a body cavity of a patient, such as the mouth, nose, anus, vagina, ears, or onto the eyes or any skin area of the patient. However, the present invention is not limited to medicinal applications and may be used wherever a precise amount of material from a pressurized fluid is to be delivered to a given region.  
         [0028]    Referring to FIG. 1, an aerosol dispensing apparatus, generally designated as  10 , is illustrated that incorporates one embodiment of a metering valve  14  in accordance with the present invention. The top end of the metering valve  14  is crimped around the end of a conventional aerosol container  12 , while a conventional discharge piece  16  is mounted around the bottom of the metering valve  14 . Thus, aerosol formulation is dispensed downwardly from the aerosol container  12 , through the metering valve  14 , then through the discharge piece  16  where it is delivered to a patient. The discharge piece  16  directs the aerosol formulation toward the body cavity or skin area to which the formulation is to be delivered. The configuration of the discharge piece  16  depends upon the application for the aerosol. For example, discharge piece  16  may be a mouthpiece that can be inserted into the patient&#39;s mouth, thereby providing oral administration of the aerosol formulation. The aerosol-dispensing device shown in FIG. 1 is merely one example of how a metering valve according to the present invention can be incorporated into a dispensing apparatus.  
         [0029]    In each of FIGS.  2 - 5 , a metering valve is shown in isolation for ease of illustration. However, the metering valves shown in these figures may be combined with an aerosol container  12 , discharge piece  16 , or both, as shown in FIG. 1.  
         [0030]    Referring to FIG. 2, the metering valve  14  is shown in the resting position. The metering valve  14  includes a housing  20  that serves to house the various components of the metering valve  14 . The top portion of the housing  20  attaches to the aerosol container  12  (as shown in FIG. 1). A valve body  22  is seated within the valve housing  20  and in turn provides a housing for a valve stem  24 .  
         [0031]    The metering valve  14  may include a spring cage  58  defining an interior chamber  38 , a portion of which is occupied by the valve stem  24 . One or more inlets  44  provide open and unrestricted fluid communication between the interior chamber  38  and the aerosol container  12 .  
         [0032]    The valve stem  24  includes two portions, identified as  24   a  and  24   b . The external portion of the valve stem  24   a  is that portion of the valve stem  24  that is positioned outside the valve housing  20  while the valve stem  24  is in the resting position shown in FIG. 2. During actuation of the valve stem  24 , however, at least some of the external valve stem  24   a  is displaced inwardly with respect to the metering valve  14 , as described more fully below, so that a portion of the external valve stem  24   a  is transiently positioned inside the valve housing  20 . The internal valve stem  24   b  is that portion of the valve stem  24  that is positioned within the valve housing  20  throughout actuation of the valve stem  24 .  
         [0033]    The external valve stem  24   a  includes a passageway through which a metered dose of formulation is discharged, as will be described more fully below. The passageway may include one or more side holes  28 , a discharge passageway  26  and a discharge opening  30 .  
         [0034]    The internal valve stem  24   b  may be configured to have substantially the same shape as, but to be slightly smaller than, the surrounding wall of the valve body  22   a . Thus, a narrow annular space  32  may be formed between the valve body wall  22   a  and the internal valve stem  24   b . In certain embodiments in which the valve stem  24  and the valve body wall  22   a  are both circular in cross-section, the narrow annular space  32  may form a ring. However, the valve stem  24  and valve body wall  22   a , and therefore the narrow annular space  32 , may be any suitable shape. The internal valve stem  24   b  includes an interior space  36  defined by the walls of the valve stem  24 . One or more channels  34  are formed in the walls of the internal valve stem  24   b  and provide fluid communication between the interior space  36  and the narrow annular space  32  through one or more channel openings  50 .  
         [0035]    In the resting position shown in FIG. 2, the internal valve stem  24   b  fits concentrically inside the valve body  22  and provides sufficient clearance for the narrow annular space  32 . Accordingly, only a small percentage of the metering chamber volume is present in the metering valve  14  while it is in the resting position shown in FIG. 2. As will be described in greater detail below, when the valve stem  24  is actuated, the valve stem  24  is displaced into the interior chamber  38  of the metering valve  14  and a space is created between the internal valve stem  24   b  and the floor of the valve body  22   b . The space thus created is the metering chamber  60 , as shown in FIG. 3.  
         [0036]    In the embodiment shown in FIG. 2, a spring  48  is provided within the interior chamber  38  of the metering valve. The spring  48  serves to bias the valve stem  24  toward the resting position shown in FIG. 2. However, any suitable means for biasing the valve stem  24  into the resting position shown in FIG. 2 may be used in connection with the present invention.  
         [0037]    The metering valve  14  also includes at least two annular gaskets, the housing gasket  54  and the metering gasket  56 . The housing gasket  54  is positioned between the valve housing  20 , the valve body  22  and the valve stem  24 , as shown in FIG. 2. The housing gasket  54  isolates the formulation in the aerosol container  12  from the exterior of the valve by forming two fluid tight seals: 1) an annular seal between the housing gasket  54  and the valve stem  24  where the valve stem extends out of the valve housing, and 2) a compressive planar or face seal between the housing gasket  54  and the housing  20 . The latter seal may be effected either with or without a sealing bead  62  on either the valve body  22  or the housing  20 .  
         [0038]    The valve body  22  may include an angled shoulder  22   c , which is best seen in FIG. 3 and is designed to support the housing gasket  54  near the valve stem  24  while functioning to direct the flow of formulation out of the metering chamber  60  during the discharge stage shown in FIG. 5. The valve stem  24  may include an angled shoulder  24   c  designed to match the profile of the valve body  22 , thereby minimizing the amount of formulation present in the metering chamber  60  in the resting position shown in FIG. 2.  
         [0039]    The metering gasket  56  may be positioned between the valve body  22 , the spring cage  58 , and the internal part of the valve stem  24   b . The metering gasket  56  transiently isolates the formulation in the metering chamber  60  from the aerosol container  12 , as shown in FIGS. 4 and 5, by forming two fluid tight seals: 1) an annular seal between the metering gasket  56  and the internal part of the valve stem  24   b , and 2) a compressive planar or face seal between the metering gasket  56  and the valve body  22  The latter seal may be effected either with or without a sealing bead  64  on either the valve body  22  or the spring cage  58 . The metering gasket  56  provides a means for terminating the flow of formulation from the aerosol container  12  to the metering chamber  60  during actuation of the valve stem  24 , as will be described in more detail below.  
         [0040]    The operation of the metering valve  14  shown in FIG. 2 is illustrated in FIGS. 3, 4 and  5 . The figures illustrate the stages of operation of the metering valve  14  and the corresponding relative positions of the valve components as a patient actuates the valve stem  24 , thereby releasing a dose of aerosol formulation. FIG. 3 shows the metering valve  14  in the filling stage, FIG. 4 shows the metering valve  14  in the filled stage, and FIG. 5 shows the metering valve  14  in the discharge stage.  
         [0041]    [0041]FIG. 3 illustrates the filling stage of the metering valve  14 . The valve stem  24  has been displaced inwardly into the interior chamber  38  against the compressive force of the spring  48 . As the valve stem  24  is displaced inwardly, the proximal end of the external stem  24   a  enters the valve housing  20  such that an annular space, the metering chamber  60 , is formed between the valve body  22  and the valve stem  24 . The volume of the metering chamber  60  increases as the valve stem is displaced. Displacement of the valve stem  24  typically continues until the valve stem  24  reaches a “filled” position, depicted in FIG. 4.  
         [0042]    The aerosol formulation enters the metering chamber  60  in the following manner. Formulation from the aerosol container  12  passes through the one or more metering valve inlets  44  and into the interior chamber  38  of the metering valve. From the interior chamber  38 , the formulation passes through the valve stem inlet port  40  and enters the valve stem interior space  36 . Formulation then passes through one or more channels  34 , one or more channel openings  50  and the narrow annular space  32 , into the metering chamber  60 . Consequently, as the valve stem  24  is moved from the resting position shown in FIG. 2 to the filling stage shown in FIG. 3, aerosol formulation passes from the aerosol container  12  to the metering chamber  60  immediately upon actuation of the valve stem  24 . Formulation continues to fill the metering chamber  60  until the metering valve  14  reaches the filled stage depicted in FIG. 4.  
         [0043]    [0043]FIG. 4 illustrates the metering valve  14  in the filled stage. The flow path of formulation from the aerosol container  12  to the metering chamber  60  becomes occluded as the metering gasket  56  moves past the channel opening  50 . Ultimately, the channel opening  50  is fully occluded by the metering gasket  56 , as shown in FIG. 4, and the flow of formulation into the metering chamber  60  is cut off, thereby concluding filling of the metering chamber  60 .  
         [0044]    Upon further actuation, the metering gasket  56  forms a fluid seal around the valve stem  24  that prevents any additional flow of formulation to the metering chamber  60 . At this stage, the metered dose of formulation is isolated and ready for discharge from the metering chamber  60  and delivery to the patient. The dimensions of the valve body  22 , valve stem  24  and other valve components determine the volume of the metering chamber  60  in the filled position depicted in FIG. 4. The valve body  22 , valve stem  24  and other valve components may be designed to permit largely unimpeded flow of formulation during the filling stage while preventing unintended continuous discharge of formulation subject to the dimension tolerances of the valve components.  
         [0045]    [0045]FIG. 5 depicts the metering valve  14  in the discharge stage of actuation. In order to discharge the metered dose of aerosol formulation from the metering chamber  60 , the valve stem  24  may be further actuated to the position illustrated in FIG. 5. The distance traveled by the valve stem  24  between FIG. 4 and FIG. 5 may result in an expansion of the metering chamber volume without adding to the metered dose of formulation because of the seal formed between the metering gasket  56  and the valve stem  24 , described above. The extra travel ensures that the metering gasket  56  is sealed against the valve stem  24  before the one or more side holes  28  enter the metering chamber  60 . This extra travel thus serves to allow for dimensional variations in the valve components.  
         [0046]    As the valve stem  24  is fully actuated, the one or more side holes  28  of the discharge passageway  26  pass through the housing gasket  54  and come into fluid communication with the metering chamber  60 . That fluid communication allows the aerosol formulation within the metering chamber  60  to be released into the one or more side holes  28  and the formulation thus passes through the discharge passageway  26  and out of the discharge opening  30 , thereby delivering the metered dose of aerosol formulation to the patient or other desired area.  
         [0047]    During the discharge of the aerosol formulation from the metering chamber  60  as shown in FIG. 5, the metering gasket  56  continues to prevent the passage of additional bulk formulation from the aerosol container  12  to the metering chamber  60 . After the dose of aerosol formulation is discharged, the patient releases the valve stem  24 , which returns to its original resting position depicted in FIG. 2 by the biasing action of the spring  48 .  
         [0048]    The successive stages of valve stem actuation depicted in FIGS. 2, 3,  4  and  5  are all accomplished during the brief duration of actuation of the valve stem  24 . Accordingly, formation, filling and emptying of the metering chamber  60  occurs rapidly. Only a small percentage of a dose of formulation resides in the metering chamber  60  between discharges, and the metering chamber  60  contains a fully metered dose of formulation only for a brief moment immediately prior to discharge of the dose from the metering chamber  60 . Subsequent release of the valve stem by the patient allows the valve to return from the position depicted in FIG. 5 to that depicted in FIG. 2.  
         [0049]    Because the valve body  22 , valve stem  24  and other valve components together define the volume of the metering chamber  60 , the metering valve components may be designed to form a metering chamber  60  having an appropriate metering volume for any desired application. Furthermore, metering valves having different capacities may be manufactured by, for example, altering the relative position of the channels  34  and channel opening  50  along the wall of the internal valve stem  24   b . The volume of the metering chamber  60  at any moment is defined, in part, by the extent to which the valve stem  24  is displaced inwardly with respect to the metering valve  14 .  
         [0050]    The volume of the metering chamber  60  at the moment that the metering gasket  56  fully occludes the channel opening  50  defines the filling capacity of the metering chamber  60 . Therefore, a metering valve in which the metering gasket  56  fully occludes the channel opening  50  relatively early in the displacement of the valve stem  24  will have a smaller filling capacity than a metering valve in which the metering gasket  56  fully occludes the channel opening  50  relatively late in displacement of the valve stem  24 .  
         [0051]    The channel opening  50  is defined by an axial dimension and a circumferential dimension as shown in FIG. 6 a . As used herein, the axial dimension, or height, is the dimension parallel to the direction of displacement of the valve stem  24  during actuation. As used herein, the circumferential dimension, or width, is the dimension parallel to the circumference of the valve stem  24 .  
         [0052]    In one embodiment, at least one channel opening  50  has a cross-sectional width that is greater than its height, thereby constituting a wide, short channel opening  50 .  
         [0053]    Certain embodiments of the present invention have a channel opening having a height of about 0.25 mm, some have a channel opening with a height of about 0.5 mm, and other embodiments may have a channel opening having any height ranging from about 0.01 mm to about 1.0 mm. Embodiments having a channel opening having a height from about 0.1 mm to about 0.8 mm have been identified as being particularly useful.  
         [0054]    Certain embodiments of the present invention may have multiple channel openings  50 . In such embodiments, the multiple channel openings may form a discontinuous functional equivalent of the channel opening  50  of the present invention even though no individual channel opening has a width greater than its height. In such an arrangement, the sum of the channel opening widths may define a cumulative width. Such embodiments having multiple channel openings  50  that define a cumulative circumferential width that is greater than the height of the openings are included in the scope of the present invention.  
         [0055]    Certain other embodiments may have a single channel opening  50  that completely encircles the valve stem  24 . In these embodiments, the width of the channel opening  50  essentially equals the circumference of the valve stem  24 . An example of such an embodiment is depicted in FIG. 6 b , which shows a view of a half section of a valve stem  24 . While the channel opening  50  completely encircles the valve stem  24 , one or more internal supports  76  join two halves of the valve stem. Sophisticated internal geometries may be manufactured by forming the valve stem  24  as two separate components that can be joined together. The components may be joined by any suitable means such as press-fitting or crimping, for example. In the embodiment shown in FIG. 6 b , a lug  74  on the upper part of the valve stem  24  fits into a corresponding hole in the lower part of the valve stem  24 .  
         [0056]    A short channel opening height maximizes the proportion of the displacement of the valve stem  24  during actuation before the metering gasket  56  begins to occlude the channel opening  50 . Thus, nearly all of the formulation enters the metering chamber  60  via steady flow before the channel opening  50  begins to be fully occluded by the metering gasket  56 . This may reduce the potential effects of actuation speed with respect to filling performance. A channel opening  50  covering a large portion of the circumference of the valve stem  24  allows a large cross-sectional area for filling the annular space  32 , thereby increasing the reliability and precision of the metering of the formulation. A channel opening having the combination of a wide circumference and short height may provide a desirable balance between maximizing the cross-sectional surface area of the channel opening and also maximizing the proportion of the distance the valve stem  24  travels before the channel opening  50  begins to become occluded by the metering gasket  56 .  
         [0057]    The relationship between height of the channel opening  50  and the width of the narrow annular space  32  also may influence the filling characteristics of the metering valve  14 . Generally, a channel opening height of about one to about five times the width of the narrow annular space  32  permits steady flow of the formulation into the metering chamber  60  until approximately one half of the channel opening  50  is occluded by the metering gasket  56 . Certain embodiments of the present invention include a channel opening height that is about three times the width of the annular space  32 .  
         [0058]    A channel opening height of greater than about five times the width of the annular space  32  may cause recirculation of flow as the metering chamber  60  fills. As used herein, recirculation refers to flow circulating or flowing back against the general direction of the flow path in a localized region within a moving fluid. Recirculating formulation may interrupt the steady flow of formulation, at least in the vicinity of the recirculating flow. This may result in at least a temporary decrease in the effective cross-sectional area of the channel opening  50  available to conduct flow of formulation, thereby reducing the rate at which formulation is allowed to flow into the metering chamber  60 .  
         [0059]    The channel  34  may intersect the channel opening  50  (the channel angle) at about a 0° angle with respect to the horizontal plane of the valve stem, as shown in FIG. 7, or at an inclined angle, as shown in FIG. 8. In one embodiment, similar to that shown in FIG. 7, the channel  34  may intersect with the channel opening  50  at about a 0° angle relative to the horizontal plane of the valve stem  24  and have a channel opening  50  measuring about 0.25 mm in height and about 280° of the valve stem circumference. An alternative embodiment may have a channel opening height of about 0.5 mm.  
         [0060]    The channel angle may range from about +90° to about −90° with respect to the horizontal plane of the valve stem. An angled channel  34  may help direct the flow formulation into the narrow annular space  32  (see FIG. 3). This, in turn, may minimize the region of low pressure that may develop as the formulation passes through the channel opening  50  and into the narrow annular space  32 . Such regions of low pressure can increase the likelihood of bubble formation within the formulation. In one embodiment, similar to that shown in FIG. 8, the channel angle may be about +45° relative to the horizontal plane of the valve stem  24  and the channel opening  50  may measure about 0.25 mm in height and about 160° of the valve stem circumference. An alternative embodiment may have a channel opening height of about 0.5 mm. Any channel angle from about 0° to and including about +90°, relative to the horizontal plane of the valve stem, may be suitable for a particular application, however.  
         [0061]    In an alternative embodiment, a channel may intersect with the channel opening  50  at an angle from about 0° to about −90° with respect to the horizontal plane may be desired in certain embodiments. Such an embodiment, similar to that shown in FIG. 9, may have a channel angle of about −45° with respect to the horizontal plane of the valve stem, for example. Drug from a suspension formulation may form a sediment between dosings. In the embodiment shown in FIG. 9, such sedimented drug may preferentially collect on the floor of interior space  36 , thereby reducing sedimentation of drug in the channels  34 , the narrow annular space  32 , or both. The sedimented drug may be more readily resuspended into the formulation from the floor of the interior space  36  than from either the channels  34  or the narrow annular space  32  when the patient shakes the inhaler. Thus, such a valve stem may promote more consistent, accurate dosing and more complete use of drugs in suspension formulations. Any channel angle from about 0° to and including about −90° may be suitable for a particular application.  
         [0062]    In certain embodiments, one or more edges  72  of the channel opening  50  may be beveled or rounded, as shown in FIG. 7. Edges  72  modified in this way may provide a smooth transition of the flow path from the channel  34  into the narrow annular space  32 . This feature also may contribute to reducing the likelihood and extent to which localized regions of low pressure will develop in the flow of formulation. Consequently, beveled or rounded edges of the channel opening  50  may help reduce the likelihood of bubble formation within the formulation.  
         [0063]    Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the a illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows.