Abstract:
A dry powder inhaler having improved aerodynamic properties for diluting, dispersing, and metering drug particles for increasing the efficiency of pulmonary drug delivery to a patient is described. The inhaler comprises, in general, a housing having an air intake, an air flow-control/check-valve, a mixing section and a mouthpiece. A cartridge loaded with a single dose of medicament can be installed in the mixing section.

Description:
[0001]    This application is a Continuation-in-Part of co-pending U.S. utility patent application Serial Number (U.S.S.N.) Ser. No. 09/621,092, filed 21 Jul. 2000; which application claims domestic priority from U.S. provisional applications U.S. S. No. 60/145,464 filed 23 Jul. 1999, entitled Dry Powder Inhaler, and U.S. S. No. 60/206,123 filed 22 May 2000, entitled Unit Dose Capsules and Dry Powder Inhaler Device. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention is in the field of drug administration inhalers having improved control over system volumetric air flow rate, medicament particle transport, particle dispersion, particle metered dosimetry and patient compliance.  
         BACKGROUND OF THE INVENTION  
         [0003]    In the early 1970&#39;s it was found that certain medicines could be administered in dry-powder form directly to the lungs by inhalation through the mouth or inspiration through the nose. This process allows the medicine to bypass the digestive system, and may, in certain cases, allow smaller dosages to be used to achieve the same results as orally ingested or injected medicines. In some cases, it provides a delivery technique that reduces side effects for medicines and interactions with other prescribed medicines, as well as providing a more rapid drug medication uptake.  
           [0004]    Inhaler devices typically deliver medicine in a liquid droplet mist or as a dry powder aerosol. Deposition of particulate matter within the human lungs is a very complex and not fully understood phenomenon. People breathe over a relatively broad tidal volume. It is known that lower transport velocities of gas-entrained particles entering the mouth avoid impaction better within the oropharyngeal cavity. This is particularly true of particles greater than one to two microns in diameter.  
           [0005]    In order for particles to remain suspended in a gas stream, their superficial transport velocity must be greater than their gravity settling velocity. For example, a 100 micron particle must have a transport gas velocity of approximately 7 ft/sec or greater for the 100 micron particle to remain in a particle/gas entrainment state. The required transport velocity for smaller particles is much less High speed particles have a greater propensity to impact and deposit on the tissue lining of the oropharyngeal cavity, as noted above. Thus, a significant number of particles are lost and will not enter the lungs, if those particles are not transported at the correct velocity.  
           [0006]    Another common problem with inhalers is that the particles agglomerate, causing clumping of particles that then adhere to the inhaler or the oral cavity, rather than entering the lungs. Most approaches to this problem have been to include a surfactant in, on or with the particles to decrease the adhesion between particles.  
           [0007]    Importantly, it should not be difficult for a patient to load the inhaler with medicine, and to easily and properly use the inhaler so that the correct dosage is actually administered. Many current dry particle inhalers fail in one or more of these important criteria.  
           [0008]    It is therefore an object of the present invention to provide inhalers which are easy to properly use, and which deliver drug powders so that the powder enters the lungs instead of adhering to the back of the throat.  
           [0009]    It is an object of the invention to provide an inhaler which will operate effectively with dry powder medicaments having particles ranging in size from about 0.5 to about 10 microns, and preferably from about 1 to about 5 microns in size.  
           [0010]    It is a further object of the present invention to provide an inhaler that can operate effectively over a broad inhalation tidal volume range of human breath.  
           [0011]    It is a still further object of the present invention to provide an inhaler which controls the volume and velocity of air flow so as to provide effective and desirable colimation, de-agglomeration and entrainment of the inhaled drug.  
           [0012]    A related object is to provide an inhaler which creates a high-shear air flow field and controlled circulating gas action to break up particle agglomeration during proper inhaler usage.  
           [0013]    A more specific object is to provide an inhaler mouthpiece which is sized and shaped to develop an air flow which will air stream entrained medicament particles through the oropharyngeal cavity.  
           [0014]    Another specific object is to provide a medicament-containing inhaler cartridge which will supply medicament for complete air entrainment and proper dispersion into the air stream.  
           [0015]    Yet another object is to provide an inhaler air-flow-controlling check valve which will straighten the air flow and limit the air flow volume and velocity to values between pre-determined maxima and minima so as to properly entrain, de-agglomerate and deliver medicament particles to the inhaler user.  
           [0016]    Other objects and advantages of the invention will become apparent upon reading the following detailed description and upon reference to the drawings. Throughout the drawings, like reference numerals refer to like parts.  
         SUMMARY OF THE INVENTION  
         [0017]    A dry powder inhaler (DPI) includes an air intake and check valve section; a mixing and cartridge section; and a mouthpiece all designed to control the volume and velocity of the inhaled air and aerosolized drug. This inhaler can be operated over a very broad inhalation tidal volume range of human breath. Several features of the inhaler provide advantageous properties, most significantly with respect to using carefully designated aerodynamic forces to dilute and de-agglomerate the medicament particles, rather than using broad high pressure forces that would contribute to relatively great particle losses in the oropharyngeal region.  
           [0018]    The inhaler intake chamber mounts a check valve bulb having a tapered bulb, bulb travel rod and biasing spring, and one or more perimeter chutes or venturis on the bulb to modulate and control the flow of air through the device. The intake further optionally includes a feedback module (not shown) to generate a tone indicating to the user when the adequate inhalation air-flow rate has been achieved.  
           [0019]    The inhaler mixing section holds a cartridge containing a dry powder medicament. The cartridge has two telescopically assembled halves, and each half has an air inlet hole or orifice-port and an air outlet hole or orifice-port. When the halves are twisted so as to align the air holes, the air stream from the check valve enters the cartridge and then picks up, fluidizes and de-agglomerates the medicament powder in the cartridge. The airflow entraining the particles then exits the cartridge and flows through the mouthpiece to the inhaler user. The cover on the mixing section can open only when the mouthpiece is at an appropriate pre-determined angle to the intake conduit. The mixing section helps to impart a cyclonic flow to air passing through the mixing chamber and cartridge.  
           [0020]    An important feature of the inhaler is the mouthpiece. The mouthpiece is integrated to the swivel joint of the mixing section, and can be rotated back into the inhaler intake section and then enclosed by a cover for storage. A mouthpiece transport conduit has the ability to expand the cross-section of the air flow, which in turn reduces the velocity of approach of the drug powder into the oral cavity. As shown in FIGS. 10, 18,  19 ,  21  and  23 , the mouthpiece is offset with respect to the centerline of the mixing cavity and mounted cartridge, and the airflow inlet from the check valve mechanism into the mixing chamber and cartridge is also offset. These tangential offsets encourage a helical airflow around the cartridge, as explained in further detail below. Initially, the tangential mouthpiece exit tube increases the velocity of the transport gas, which in turn inducts the discharged particles into the exit tube. The mouthpiece exit tube then expands in one dimension and the transport gas slows while the particle concentration per unit volume becomes more dilute. Flow is expanded to create a secondary shear flow, which helps to further de-agglomerate particles. This also creates a horizontal aspect ratio and therefore aerosol discharge path that is more effective in negotiating and streaming the aerosol through the convoluted pathway of the oral pharynx.  
           [0021]    The mouthpiece expansion wall divergence angle is important for stable particle transport conditions to exist. An optimum divergence angle is between 14 and 16 degrees. However, a slightly larger 17 degree divergence angle can be used to achieve a horizontal aerosol discharge path with a 3:1 aspect ratio closely approximating the aspect ratio at the rear of the human throat. Once the expansion divergence has reached a specified limit, the continuing slot discharge tube maintains the proper collimation of the particles for controlled particle injection speed and direction of the path of the particles into the oral cavity. The mouthpiece includes a tongue depressor, and a tactile protrusion to contact the lips of the user to tell the user that the Dry Powder Inhaler (DPI) is in the correct position.  
           [0022]    The cartridge halves can be twisted into and out of positions in which the air inlet holes and the air outlet holes are respectively aligned. The cartridge can only be inserted into the mixing chamber when a cartridge alignment boss is aligned with a receiving recess at the bottom of the mixing chamber, and a cartridge collar and engages a mating mixing chamber collar (FIG. 2). Each cartridge has a unique key on each half that fits only with a particular part of the inhaler, thereby insuring that the proper cartridge containing the proper medicament is preselected, and further insuring that the cartridge is installed properly in the inhaler. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0023]    [0023]FIG. 1 is an isometric view of the inhaler embodying the invention.  
         [0024]    [0024]FIG. 2 is an exploded view of the inhaler shown in FIG. 1.  
         [0025]    [0025]FIG. 3, including FIGS. 3 a ,  3   b  and  3   c , is a front isometric view of the medicament containing cartridge used with the inhaler, showing cartridge outlet hole or orifice port alignments.  
         [0026]    [0026]FIG. 4, including FIGS. 4 a ,  4   b  and  4   c , is a rear isometric view of the medicament-containing cartridge used with the inhaler shown in FIG. 3, showing inlet hole or orifice port alignments.  
         [0027]    [0027]FIG. 5 is a front elevational view of the cartridge shown in FIGS. 3 and 4.  
         [0028]    [0028]FIG. 6 is a rear elevational view of the cartridge shown in FIGS. 3, 4 and  5 .  
         [0029]    [0029]FIG. 7 is a sectional view taken substantially in the plane of line  7 - 7  in FIG. 5.  
         [0030]    [0030]FIG. 8 is a sectional view taken substantially in the plane of line  8 - 8  in FIG. 7.  
         [0031]    [0031]FIG. 9 is a sectional view taken substantially in the plane of line  9 - 9  in FIG. 7.  
         [0032]    [0032]FIG. 10 is a top plan view of the inhaler shown in FIGS. 1 and 2.  
         [0033]    [0033]FIG. 11 is a sectional view taken substantially in the plane of line  11 - 11  in FIG. 10.  
         [0034]    [0034]FIG. 12 is a sectional view taken substantially in the plane of line  12 - 12  in FIG. 10.  
         [0035]    [0035]FIG. 13 is an isometric view of the inhaler shown in FIGS. 1 and 2 but configured for the insertion or removal of a medicament-containing cartridge.  
         [0036]    [0036]FIG. 14 is an isometric view similar to FIG. 13 but configured as it appears when a medicament-containing cartridge has been inserted in the inhaler.  
         [0037]    [0037]FIG. 15 is a sectional view taken substantially in the plane of line  15 - 15  in FIG. 13.  
         [0038]    [0038]FIG. 16 is a sectional view taken substantially in the plane of line  16 - 16  in FIG. 14.  
         [0039]    [0039]FIGS. 16 a ,  16   b  and  16   c  are fragmentary sectional views taken substantially in the plain of line  16   a - 16   c  in FIG. 16.  
         [0040]    [0040]FIG. 17 is an isometric view showing the inhaler of FIGS. 1 and 2, parts being broken away to permit the diagramming of air flow through the inhaler.  
         [0041]    [0041]FIG. 18 is an isometric view similar to FIG. 17 diagramming air flow through and around the inhaler check valve, mixing section, cartridge and mouthpiece.  
         [0042]    [0042]FIG. 19 is an isometric view similar to FIG. 18 diagramming air flow through and around the inhaler check valve, inside the cartridge, and through the mouthpiece.  
         [0043]    [0043]FIG. 20 is an isometric view similar to FIGS. 1, 2,  17 ,  18  and  19  showing the inhaler, the inhaler flow-control/check-valve, and the flow-control/check-valve sub-housing.  
         [0044]    [0044]FIG. 21 is a top plan view of the inhaler shown in FIG. 20.  
         [0045]    [0045]FIG. 22 is a sectional view taken substantially in the plane of line  22 - 22  in FIG. 21.  
         [0046]    [0046]FIG. 23 is a top plan view substantially similar to FIG. 21.  
         [0047]    [0047]FIG. 24 is a sectional view taken substantially in the plane of line  24 - 24  in FIG. 23.  
         [0048]    [0048]FIG. 25 is an isometric view of the flow-control/check-valve and sub-housing shown on FIGS. 17, 18,  19 ,  20 ,  22  and  24 . 
     
    
       [0049]    While the invention will be described in connection with several preferred embodiments and procedures, it will be understood that it is not intended to limit the invention to these embodiments and procedures. On the contrary, it is intended to cover all alternatives, modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0050]    An improved inhaler has been developed which has several novel features optimizing performance. Medicament particles can be delivered/administered over a broad range of inhalation velocity and tidal volume of human breath. An inhaler mouthpiece exit tube dilutes, expands, and collimates the particle dispersoid so that the particles do not re-agglomerate during delivery. This inhaler provides the means to effect a process whereby particles are fluidized, suspended, then scavenged from the walls by re-circulating scrubbing air, as well as higher speed-flow-through air, followed by a high-shear flow field discharge into an expanded, slower-moving mass of air that disperses and meters the particle concentration expelled from the unit dose cartridge upper outlet port.  
         [0051]    Inhaler Overview  
         [0052]    [0052]FIG. 1 shows an embodiment of a dry powder inhaler  10  described and claimed herein. In broad conceptual terms, an inhaler housing  15  includes an intake section  20 , a mixing section  30  and a mouthpiece  40 . In the preferred embodiment, this inhaler housing  15  is approximately 93 mm long, 38 mm high, and 22 mm thick. The other parts illustrated and described here are of proportionate size. The mouthpiece  40  can be swiveled from a stored position within the housing  15  to a cartridge installation position in which the mouthpiece  40  is oriented at 90 degrees to the long dimension of the housing. When a cap  352  is closed, the mouthpiece can then be further rotated into an operating position in which the mouthpiece is located at a 180 degree position to the long dimension of the housing. When the mouthpiece  40  is stored within the inhaler  15 , a sliding dirt shield cover  16  slidably mounted stored on the housing can be slid upwardly to protect the mouthpiece  40  and the air intake conduit entrance of the inhaler. The housing  15  can be formed of a gamma radiation-proof polycarbonate plastic for the rapid sterilization of the inhaler in mass production, as well as in clinical-hospital use.  
         [0053]    An air passage  50  (FIG. 17) extends through the intake section  20 , the mixing section  30  and the mouthpiece  40 . A swivel joint  80  (FIGS. 2 and 17) connects the mouthpiece  40  to the mixing section  30 . In the preferred embodiment, the mouthpiece and mixing section are one unit, and are connected by a swivel joint to the main housing. The cap  352  is pivotally attached to the mixing section  30 , and an interlock mechanism  355  prevents the mouthpiece  40  from being swung into an operating position unless the cartridge  301  is properly seated and installed. A cartridge  300  shown in FIGS. 3, 4 and  5  contains a medicament powder, and it can be installed in and removed from the mixing chamber  30 .  
         [0054]    Aerosolized powder is drawn from the cartridge  301  and mixing section  30  through the mouthpiece  40  to the users&#39; oropharangeal cavity via the mouthpiece  40 . As air and powder travel through the mouthpiece, the velocity of the travel slows, thus preparing the powder for effective delivery to the inhaler user&#39;s broncheal tract and lungs.  
         [0055]    So that writing or identifying indicia on medicament-containing cartridge  301  can be read easily, the mixing section  30  has a cover  352  which may be configured as a transparent magnifying lens. An arrow  460  (FIG. 17) shows the direction of aerosolized medicament powder discharge from the cartridge and through the mouthpiece.  
         [0056]    Air is caused to enter the inhaler by an inhalation effort which the inhaler user exerts on and in the mouthpiece  40 . As shown particularly in FIG. 17 and as suggested by the air-flow arrows  460  in FIGS. 17 and 18, ambient air enters the air control system  171  through air intake ports  172  and is directed to an air flow-control/check-valve  180 . As shown in FIGS. 17, 18, and  25 , this check valve system  180  includes a conical head  181  mounted upon a bulb rod  182 . A bulb  184  is slidably mounted upon the rod  182  for reciprocation between a stagnant air-flow position and a dynamic air-flow-inhibiting position. The bulb  184  is drawn into a normal relatively downstream air-flow position, by the force of air flow acting to overcome the bulb reactive force of a conical tension spring  185  as suggested particularly in FIG. 19. This spring is preferably formed of medical grade stainless steel. Chute-like recesses  186  in the surface  187  of the bulb  184  control and direct the flow of air over the bulb  184 . Air-flow straightening vanes  189  mounted on the conical head  181  engage a confronting conical venturi formation or seat  191  (FIG. 22). Air flowing between the head  181  and seat  191  is accelerated and the air-flow straightened, in accordance with known characteristics of gaseous air-flow.  
         [0057]    When the inhaler user draws air through the mouthpiece  40 , air flows to and around the bulb  184 , and the imbalance of air pressure forces acting upon the reciprocating bulb  184  pushes the bulb in a downstream direction along the rod  182  into positions which inhibits air-flow. Because the bulb  184  is mounted to the tension spring  185 , increasing amounts of force are required to draw the bulb  184  into increasingly air-flow-restricting positions. Additional bulb movement control can be provided, if desired, by an opposing second spring (not shown) forming a high-sensitivity push-pull system.  
         [0058]    This bulb and spring mechanism allow the inhaler user to generate a slight partial vacuum in his lungs before the bulb is drawn away from the seating arrangement. Thus, by the time significant vacuum is generated, a slight velocity increase of air-flow through the inhaler assists in drawing the medicament from the cartridge (FIGS. 1 and 17- 19 ), through the inhaler and into the bronchial region and lungs of the user.  
         [0059]    As suggested particularly in FIG. 20, the check valve arrangement  180  can be mounted in a sub-housing  20 , and both components  20  and  180  can be removed from the inhaler housing  50  for cleaning, repair or replacement. A lock device  196  of known design can be used to secure the sub-housing  20  and contained components within the inhaler housing  50 .  
         [0060]    When air is being drawn through the inhaler  10  and the bulb  184  is drawn along the rod  182  so as to impact the conical head  181 , a clicking sound is produced. In accordance with one aspect of the invention, this clicking sound indicates to the inhaler user that he or she is drawing properly upon the mouthpiece and operating the inhaler correctly. If desired, a vibratory mechanical reed (not shown) can be mounted in the air-flow path to produce an audible signal to the user. Alternatively, an electronic flow or pressure sensor can trigger an audible or visual signal indicator to tell the user that proper air flow has been established.  
         [0061]    This air flow-control/check-valve system  180  serves to deliver air at a predetermined volume and velocity to downstream inhaler parts. The air-flow, at this predetermined volume and velocity, acts to pick-up, fluidize, de-agglomerate and deliver entrained medicament particles to the inhaler user in a dispersed form and at a proper location to enter the user&#39;s bronchial system.  
       Venturi and Mixing Section  
       [0062]    As suggested particularly in FIGS. 12, 17 and  18 , the air flow is then drawn through a venturi passage  201  of restricted size, thus increasing the velocity of that air-flow, and into the inhaler mixing section  30 . As shown in FIGS. 10-17, this mixing section  30  here comprises a fixed support  31  upon which is journaled a cup  32 . It will be noted that the mouthpiece  40  is attached to the swivel cup  32  and can thus act as a handle for pivoting the cup member  32  and mouthpiece to the configurations shown in FIGS. 1, 14 and elsewhere and as more fully described below.  
         [0063]    In general, the mixing section  30  is provided with shapes on its interior surface to encourage air flow acceleration so as to suspend medicament particles in the air-flow and to de-agglomerate them. Within the cup  32  a medicament-containing cartridge  301  can be mounted. As more fully described below, the cartridge  301  is provided with air inlet and outlet holes (FIGS. 5-9), the cup  32  is sized and shaped so as to direct air into the cartridge through the lower inlet hole. The air then generally flows up through the cartridge in an upward direction while producing a dual counter-rotating helical motion, and out of the cartridge and down the mouthpiece as particularly suggested in FIG. 19. As suggested in FIG. 18, excess volume of air can flow around the outside of the cartridge but within the mixing chamber to again mate with the emerging medicament-laden air discharged from the cartridge and flowing into the mouthpiece. Thus, air flowing into the mixing chamber feeds the cartridge inlet holes, helps to extract air flowing out from the cartridge discharge holes, dilutes the medicament-laden air flow, and provide controlled, even concentrations of medicament particles into the mouthpiece air flow. The particle entrainment and dilution in the mouthpiece are provided primarily by the cartridge bypass air.  
         [0064]    As suggested in FIGS. 11, 12,  15  and  16 , the mixing chamber inlet port  33  provides vortex shedding which, aided by the top and bottom internal mixing chamber internal swirl toroids  34  and  35 , fluidizes, suspends and scrubs the powder in the cartridge. The upper semi-toroid shape  35  changes air flow direction from dispersion chamber to mouthpiece, thus aiding further de-agglomeration of the medicament particles in the entrained powder stream. To reduce powder cohesion, a modest gas expansion velocity with subsequent air shearing forces (and flow resistance) act to support a fully dispersed flow through  40 .  
         [0065]    Alternatively, a chamber which includes internal protrusions or spiral shapes can be provided. The interior surfaces of the mixing chamber can be shaped to provide one or more helical flows of air around and within the cartridge, if desired.  
       Cartridge  
       [0066]    The cartridge  301  is shown in further detail in FIGS. 3-9. In the illustrated embodiment, the cartridge  301  comprises an upper half  302  and a lower half  303 , each preferably formed of transparent plastic material. To encourage medicament particle dispersion, the preferable plastic material is provided with ultra smooth surfaces, is capable of being molded into the cartridge components which have and which maintain great dimensional accuracy, does not absorb or otherwise interact with water or moisture, and has electrostatically neutral characteristics such that the medicament powder in the cartridge  301  is not retained by cartridge static charge, and does not adhere to the cartridge halves  302 ,  303 . One such material which can be used for the lower half  303  is the Topaz brand of cyclicolephin co-polymer plastic offered by Ticonia Corporation.  
         [0067]    The upper cartridge half  302  defines an air inlet hole  306  and an outlet hole  307 , and the cartridge lower half defines a corresponding air inlet hole  308  and an air outlet hole  309 . This upper half can be made of a clear very low water absorbent nylon. As shown particularly in FIG. 7, and as suggested in FIG. 3 a , the halves  302  and  303  interengage through a telescopic fit. A circumferential ring and groove arrangement  310  retain the halves  302  and  303  in their assembled configuration.  
         [0068]    As suggested particularly in FIGS. 5, 6,  8 , and  9 , the inlet holes  306  and  308  formed at the lower portion of the cartridge are beveled, and the outlet holes  307 ,  309  are likewise beveled at an angle of substantially 60 degrees so as to encourage air ingress and egress but to discourage electrostatic adhesion and agglomerate deposition of 10 or larger micron-sized medicament particles on the plastic defining the hole edges. To enable air flow and particle pickup action, the inlet holes  306  and  308  are arranged to overlap or register with one another when the cartridge halves are twisted (as suggested by the arrow A in FIG. 4 c ) into the appropriate cartridge open position, and the holes  306 ,  308  are elongated in a vertical direction. Similarly, the outlet holes  307 ,  309  are arranged to overlap and provide free air egress when the cartridge halves are appropriately aligned, and the holes are elongated in a horizontal direction so as to orient the air outflow for delivery to the horizontally elongated channel in the mouthpiece  40 .  
         [0069]    This cartridge  301  is approximately one-quarter inch in diameter and its body is approximately 1 inch in axial length, and so to facilitate easy installation and extraction from the inhaler  10 , a handle or manipulator structure  314  is provided atop the cartridge  301 . Here, the handle structure  314  comprises four web extensions  315  which extend from the cartridge body to a finger disk  316  which may have a coined or serrated periphery. A pointer or dial indicator  317  is formed atop the disk  316  and is further discussed below.  
         [0070]    At the bottom of the cartridge  301 , a cartridge installation check boss  319  is formed. In accordance with another aspect of the invention, this check boss can have a unique, non-circular shape of any desired form such as those shown in FIGS. 16 a ,  16   b  and  16   c . These unique embossments are designed to fit within a closely mating relief  39  formed in the base  31  of the mixing section. These unique embossed shapes will be uniquely associated with particular medicaments, so that a cartridge containing an incorrect medicament cannot be installed in a particular patient&#39;s inhaler.  
       Cartridge Mounting Mechanism  
       [0071]    To properly mount the cartridge  310  in the inhaler  10 , a mounting mechanism  350  is provided as especially shown in FIGS. 1, 2,  13 - 16  and  17 . This mounting mechanism  350  takes the form of a cap  352  formed of clear plastic, pivotally mounted so as to cover the mixing section cup  32 . See especially FIG. 16. A pivot pin  353  interconnects the cap  352  with an extension  354  of the mount  31 . To facilitate reading indicia marked upon the top of the cartridge pointer  317 , the top of this cap  352  is curved so as to act as a magnifying lens. This dome shape also provides strength to the cover structure.  
         [0072]    The cartridge can be installed and the cap  352  secured in place when the mouthpiece  40  and cartridge are pivoted into their operating positions. To this end, a radially outwardly biased lock pin  356  (FIG. 2) depending from the cap mount  31  pushes the cap  352  upwardly and into an open position when the mouthpiece  40  and cap mount  31  are swiveled into a position so that the mouthpiece is located at approximately 90 degrees to the long or greater dimension of the inhaler body  15 . In this configuration, the lock pin  356  is pushed radially outwardly and the cap  352  is rotated upwardly when the lock pin  356  is pushed into a relief  359  defined in a skirt  360  of the cover  358  (FIG. 2). This arrangement acts as a safety and user prompting feature.  
         [0073]    After the cartridge is inserted into the inhaler and the cap is closed, the mouthpiece  40  can be pivoted out of its cartridge installation and cap release position as shown in FIGS. 13-16 and into the user medication inhalation configuration shown in FIGS. 1, 17 and  20 - 24 . This mouthpiece pivoting motion can occur only when the cap skirt  360  is pushed down into its closed position and the lock pin  356  is radially depressed so as to permit mouthpiece  40  swiveling action. Thus, when the inhaler user moves the mouthpiece from its stored position within the housing  15  to the cap unlocked position, the cap springs open as shown in FIGS. 13 and 15, and thereby indicates to the inhaler user that he or she should inspect and, if necessary, replace or insert a new cartridge  301 .  
       Mouthpiece  
       [0074]    As suggested above, the mouthpiece  40  discharges particle-laden air to the oropharyngeal cavity of the user. In addition, the mouthpiece diverges the air and particle stream to slow down the particles, and then converges the particle stream to collimate and aim the particles at the rear of the user&#39;s mouth. The mouthpiece is long enough so that it extends approximately midway into most users&#39; mouths. To encourage correct inhaler and mouthpiece usage, the inhaler mouthpiece is oriented so as to extend diagonally upwardly at approximately a 3 degree angle X as suggested in FIGS. 22 and 24. As suggested in FIGS. 21 and 23, the horizontally spaced walls of the mouthpiece diverge at an angle Y of approximately 5 to 8 degrees. As suggested by a comparison of FIGS. 21 and 22, the ratio of the height H of the mouthpiece air passage page to the width W of the air passage is approximately 3:1. If desired, a tooth and lip placement embossment  411  can be provided to depend from the distal end  412  of the mouthpiece  40 . The mouthpiece is preferably made of Delrin or Celcon co-polymer acetyl plastic so as to provide proper strength, swivel bearing self-lubricity, and smooth internal and external finish.  
         [0075]    In use, the inhaler employs a regulated flow of air to fluidize and aerosolize medicament particles and transport them to the desired rear region of the orophalangeal cavity. To accomplish this, air is first drawn into the interior of the inhaler housing  15  and through the intake ports  172  as suggested in FIGS. 17 and 18, to a predetermined volumetric air flow which is controlled by the flow-control/check-valve mechanism  180 . The airstream then enters into the cartridge interior through the vertically elongated and aligned inlet ports  306 . The air entering the cartridge interior immediately impinges upon the opposite cylindrical cartridge wall. The impacted air jet then redistributes itself into several portions. One of the portions flows downwardly into the medicament powder bed, and strips the powder from the cartridge surface and begins to fluidize it into an airborne dust cloud. Another portion of the impingement jet is directed laterally in both directions, which creates dual counter-rotating vertical spinning helical columns. The majority of the fluidized medicament powder is retained in these two columns, where the first deagglomeration action is achieved. Yet another portion of the impingement jet is directed vertically, which creates a vertical high-speed air jet along the cartridge wall into the cartridge discharge port or holes  306 ,  309 . Particles in the helical aerosolized columns are scavenged into the jetstream and then discharged from the cartridge. This scavenging effect results in particles being metered out or discharged from the cartridge at a relatively steady particle distribution rate. Particle agglomerations are further broken down by the discharge process. Large agglomerates impinge upon the opposing mixing chamber wall, and are further reduced into smaller agglomerates. Single particles and smaller agglomerates are carried forward through the mixing chamber and into the mouthpiece discharge tube. The remaining agglomerates are pulled apart in the high-shear and shock flow field produced by the mouthpiece tangential entry port. Thus a steady flow of a individual medicament particles emerge from the mouthpiece and into the users oropharyngeal airway. These airstream flows and the sub-stream flows thus result in complete air entrainment of all medicament particles in the cartridge, and delivery of a complete, closely metered medicament dose to the patient.