Abstract:
A medicament delivery device for administering a medicament to a user includes a medicament reservoir and an entrance port and an exit port each disposed adjacent the reservoir. A gas chamber disposed adjacent the entrance port. The device includes a pressurizing mechanism operable to pressurize said gas chamber to at least a prescribed pressure. A first frangible membrane extends across the entrance port and separates the reservoir from the gas chamber. A second frangible membrane extends across the exit port. When the pressurizing mechanism is attached, at least one of the first and second membranes is responsive to the prescribed pressure in the gas chamber to burst to allow gas to flow through the entrance port and the reservoir and to carry the medicament through the exit port.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a continuation application Ser. No. 11/369,596, filed Mar. 7, 2006 now U.S. Pat. No. X,XXX,XXX of which is a continuation of Ser. No. 10/792,583, filed Mar. 3, 2004, now U.S. Pat. No. 7,040,316 which is a continuation application of Ser. No. 09/758,776, filed Jan. 12, 2001, now U.S. Pat. No. 6,722,364 each of which are herein incorporated by reference in their entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to medicament delivery devices and, more particularly, to devices for administering inhalable medicaments. 
       BACKGROUND OF THE INVENTION 
       [0003]    Inhalers are commonly used to deliver various medicaments to users via the user&#39;s nose or mouth. Such medicaments increasingly include dry powders. A number of considerations affecting the efficacy of delivery may be presented, particularly in the case of dry powders. For example, it may be important to ensure that the appropriate dose is metered and expressed, that the medicament is properly dispersed in the conveying fluid (e.g., the carrier gas), that the delivery device is not unduly susceptible to user error in operation, and/or that undue inhalation strength is not required. Further considerations may include the operating complexity, portability and size of the delivery device. Because inhalation therapy often requires numerous applications, the cost of providing the dosage may be of particular importance. 
       SUMMARY OF THE INVENTION 
       [0004]    According to embodiments of the present invention, a medicament delivery device for administering a medicament to a user includes a medicament reservoir and an entrance port and an exit port each disposed adjacent the reservoir. A gas chamber is disposed adjacent the entrance port. The device includes a pressurizing mechanism operable to pressurize the gas chamber to at least a prescribed pressure. A first frangible membrane extends across the entrance port and separates the reservoir from the gas chamber. A second frangible membrane extends across the exit port. When the pressurizing mechanism is attached, at least one of the first and second membranes is responsive to the prescribed pressure in the gas chamber to burst to allow gas to flow through the entrance port and the reservoir and to carry the medicament through the exit port. 
         [0005]    The pressurizing mechanism may include a compressible blister defining the gas chamber and operable to pressurize the gas chamber to at least the prescribed pressure. The device may include: a first sheet including the compressible blister formed therein; a second sheet defining the reservoir therein; and an intermediate layer disposed between the first and second sheets, the first and second membranes forming a part of the intermediate layer. 
         [0006]    According to further embodiments of the present invention, a medicament delivery device for administering a medicament to a user includes a medicament reservoir and an entrance port and an exit port each disposed adjacent the reservoir. The device includes a compressible blister defining a gas chamber and operable to pressurize the gas chamber to at least a prescribed pressure. A frangible membrane extends across the entrance port and separates the reservoir from the gas chamber. When the blister is compressed, the membrane is responsive to the prescribed pressure in the gas chamber to burst to allow gas to flow through the entrance port and the reservoir and to carry the medicament through the exit port. 
         [0007]    According to further embodiments of the present invention, a method for administering a medicament to a user includes providing a medicament delivery device including: a medicament reservoir; an entrance port and an exit port each disposed adjacent the reservoir; a gas chamber disposed adjacent the entrance port; a pressurizing mechanism operable to pressurize the gas chamber to at least a prescribed pressure; a first frangible membrane extending across the entrance port and separating the reservoir from the gas chamber; and a second frangible membrane extending across the exit port. The pressurizing mechanism is actuated to generate the prescribed pressure in the gas chamber, whereupon at least one of the first and second membranes bursts to allow gas to flow through the entrance port and the reservoir and to carry the medicament through the exit port. 
         [0008]    According to further embodiments of the present invention, a method for administering a medicament to a user includes providing a medicament delivery device including: a medicament reservoir; an entrance port and an exit port each disposed adjacent the reservoir; a compressible blister defining a gas chamber and operable to pressurize the gas chamber to at least a prescribed pressure; and a frangible membrane extending across the entrance port and separating the reservoir from the gas chamber. The blister is compressed to generate the prescribed pressure in the gas chamber, whereupon the frangible membrane bursts to allow gas to flow through the entrance port and the reservoir and to carry the medicament through the exit port. 
         [0009]    Objects of the present invention will be appreciated by those of ordinary skill in the art from a reading of the figures and the detailed description of the preferred embodiments which follow, such description being merely illustrative of the present invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]    The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, serve to explain principles of the invention. 
           [0011]      FIG. 1  is a perspective view of a delivery device according to embodiments of the present invention; 
           [0012]      FIG. 2  is an exploded, perspective view of a dispenser forming a part of the delivery device of  FIG. 1 ; 
           [0013]      FIG. 3  is a center cross-sectional view of the dispenser of  FIG. 2 ; 
           [0014]      FIG. 4  is a center cross-sectional view of the dispenser of  FIG. 2  wherein the dispenser is in a partially actuated position; 
           [0015]      FIG. 5  is a perspective view of an intermediate sheet of a dispenser according to a further embodiment of the present invention; 
           [0016]      FIG. 6  is an exploded, perspective view of a dispenser according to a further embodiment of the present invention; 
           [0017]      FIG. 7  is a center cross-sectional view of a dispenser according to a further embodiment of the present invention; 
           [0018]      FIG. 8  is a center cross-sectional view of the dispenser of  FIG. 7  wherein a cap thereof is removed; 
           [0019]      FIG. 9  is a center cross-sectional view of a dispenser according to a further embodiment of the present invention; 
           [0020]      FIG. 10  is a center cross-sectional view of a dispenser according to a further embodiment of the present invention, wherein the dispenser is shown in a partially actuated position; 
           [0021]      FIG. 11  is a center cross-sectional view of a dispenser according to a further embodiment of the present invention, wherein the dispenser is shown in a partially actuated position; 
           [0022]      FIG. 12  is a side elevational view of a dispenser according to a further embodiment of the present invention; 
           [0023]      FIG. 13  is an exploded, perspective view of the dispenser of  FIG. 12  prior to assembly; 
           [0024]      FIG. 14  is a perspective view of a delivery device according to a further embodiment of the present invention, wherein a delivery tube thereof is in a folded position; 
           [0025]      FIG. 15  is a perspective view of the delivery device of  FIG. 15 , wherein the delivery tube thereof is shown in an extended, operative position; 
           [0026]      FIG. 16  is a perspective view of a delivery device according to a further embodiment of the present invention, wherein a delivery tube thereof is shown in an extended position; 
           [0027]      FIG. 17  is a perspective view of the delivery device of  FIG. 16 , wherein the delivery tube thereof is shown in a retracted position; 
           [0028]      FIG. 18  is a perspective, fragmentary view of a delivery device according to a further embodiment of the present invention; 
           [0029]      FIG. 19  is a perspective, schematic view of a delivery device according to a further embodiment of the present invention; and 
           [0030]      FIG. 20  is a perspective, fragmentary view of a delivery device according to a further embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0031]    The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. In the figures, certain components and the thicknesses of some layers may be exaggerated for clarity. 
         [0032]    With reference to  FIGS. 1-4 , a medicament inhalation delivery device  101  according to embodiments of the present invention is shown therein. The delivery device  101  includes a dispenser  100  and a delivery tube  180  (see  FIG. 1 ). The dispenser  100  includes a pressurizing mechanism  110 , a storage volume  116  and a diffuser tube  120 . The dispenser  100  contains a quantity of a desired medicament  5  (see  FIG. 3 ) in the storage volume  116 . Preferably, the quantity of medicament corresponds to a single therapeutic dose. The medicament  5  may be a sterile, dry powder medicament. 
         [0033]    Generally, and as discussed in greater detail below, the medicament  5  may be delivered to the airway of the user, typically to the mouth or nose of the user by locating the free end of the delivery tube  180  adjacent the user&#39;s mouth or nose and actuating the pressurizing mechanism  110 . In this manner, a carrier gas  111  is forced through the storage volume  116 , the diffuser tube  120  and the delivery tube  180 . As the carrier gas  111  flows through the storage volume  116 , the medicament  5  becomes entrained in the gas  111  and is transported and expelled from the delivery tube with the gas to the user. Optionally, the delivery tube  180  may be omitted, in which case the open end of the diffuser tube  120  may be directly located adjacent the mouth or nose of the user. 
         [0034]    As best seen in  FIGS. 2 and 3 , the dispenser  100  includes an upper sheet  140 , a lower sheet  160  and an intermediate sheet  150 . The relative thickness of the intermediate sheet  150  is exaggerated in  FIGS. 3 and 4  for clarity. The upper sheet has a blister  142  and a cone-shaped channel  144  formed therein. The blister  142  and the channel  144  are surrounded by marginal portions  146 A,  146 B and  146 C ( FIG. 3 ). The lower sheet  160  has a reservoir  166  formed therein and marginal portions  162 ,  164  surrounding the reservoir  166 . 
         [0035]    The sheets  140 ,  150 ,  160  are relatively configured and disposed such that the upper sheet  140  is joined to the intermediate sheet  150 , and thereby to the lower sheet  160 , by the marginal portions  146 A and  146 C (see  FIG. 2 ). While the intermediate sheet  150  is shown as extending the full length of the dispenser  100 , the intermediate sheet  150  may be abbreviated and may comprise multiple, discrete sheets. For example, one such sheet may include the membrane  152  as described below and another, separate such sheet may include the membrane  154  as described below. 
         [0036]    A central portion  146 B of the upper sheet  140  is laminated to the intermediate sheet  150  and overlies the reservoir  166 . The length D of the reservoir  166  is greater than the length C of the central portion  146 B so that an entrance opening or port  114  and an exit opening or port  118  are defined on either side of the central portion  146 B. The ports  114  and  118  have lengths A and B, respectively. The intermediate sheet  150  includes a first or entrance membrane  152  (indicated by dashed lines in  FIG. 2 ) which extends fully across the port  114 . The intermediate sheet  150  also includes an exit membrane  154  (indicated by dashed lines in  FIG. 2 ) which extends fully across the port  118 . In this manner, the reservoir  166 , the entrance membrane  152 , the exit membrane  154  and the central portion  146 B define the reservoir  166  within which the medicament  5  is fully encapsulated in the storage volume  116 . 
         [0037]    The blister  142  and the marginal portion  162  form the pressurizing mechanism  110  and define a gas chamber  112 . The gas chamber  112  is disposed immediately adjacent the port  114  and is fully sealed from the storage volume  116  by the entrance membrane  152 . Similarly, the channel  144  and the marginal portion  164  form the diffuser tube  120  and define a passage  122  and a delivery opening  124 . The passage  122  is disposed immediately adjacent the port  118  and is fully sealed from the storage volume  116  by the exit membrane  154 . 
         [0038]    The upper and lower sheets  140 ,  160  are preferably thermoformed from a suitable polymeric or elastomeric material. More preferably, the upper and lower sheets  140 ,  160  are formed of a co-laminated or co-extruded film including a layer of thermoformable polyethylene terephthalate (PET) on the exterior thereof and a layer of heat-sealable polyethylene on the interior thereof. The intermediate layer  150  is preferably formed of a layer of polyethylene. Preferably, the intermediate layer  150  has a thickness of between about ½ and 4 mil. Preferably, the intermediate layer  150  has a burst pressure of between about 4.4 and 89.0 Newtons. Preferably, the intermediate layer  150  has a tensile strength of between about 10 and 50 MPascals. 
         [0039]    The gas chamber  112  preferably has a volume of between about 0.2 and 10 milliliters. The gas in the gas chamber  112  and the gas in the storage volume  116  can be the same or different gases. These gases may be air or other suitable gases. For example, noble gases, N 2 , Ar or He may be used. 
         [0040]    The medicament  5  may be any substance which produces a clinically useful result. By “clinically useful result” is meant clinically adequate prevention or treatment of a disease or condition by administration of a substance. Examples include, but are not limited to, clinically adequate control of blood sugar levels (insulin), clinically adequate management of hormone deficiency (PTH, Growth Hormone, etc.), expression of protective immunity (vaccines), prevention of thrombosis (heparin or derivatives), alleviation or prevention of pain (antimigraines, opiods, etc.), infection control (antibiotics), allergy control, or clinically adequate treatment of toxicity (antitoxins). More preferably, the medicament  5  is a dry powder consisting of a substance producing a clinically useful result. Such substances may be incorporated as components of mixtures with other excipients by processes which are known in the art. Such processes may include, but are not limited to, freeze drying of mixtures followed by dry blending, spray drying and supercritical processing methods. 
         [0041]    The dispenser  100  (or a series of dispensers  100 ) may be formed on a web in a manner similar to that commonly employed to form blister packs. The blister  142  and the channel  144  are thermoformed in a web corresponding to the upper sheet  140 , and the reservoir  166  is thermoformed in a web corresponding to the lower sheet  160 . A web corresponding to the intermediate sheet  150  is inserted between the webs corresponding to the sheets  140  and  160 . The webs corresponding to the sheets  140 ,  150  and  160  are then heat sealed in the layered configuration as shown in  FIG. 3  with the medicament  5  disposed in the reservoir  160 . Preferably, the medicament  5  is first placed in the reservoir  166 , the web corresponding to the sheet  150  is thereafter heat sealed to the web corresponding to the sheet  160  to package the medicament  5 , and the web corresponding to the sheet  140  is thereafter heat sealed to the opposite side of the web corresponding to the sheet  150  to form a unitary dispenser  100 . The dispenser  100  is then die cut or otherwise severed from the remainder of the webs. 
         [0042]    For inhalation through the nose, the dispenser  100  is preferably used without the delivery tube  180 . For inhalation through the mouth, the dispenser  100  may be mounted in the opening  182 B of the delivery tube  180  by means of slots  184  ( FIG. 1 ). The delivery opening  182 A of the delivery tube  180  is placed adjacent the user&#39;s mouth or, alternatively, the delivery opening  124  of the diffuser tube  120  is placed adjacent the user&#39;s nose. Preferably, in operation, the dispenser  100  is oriented such that the blister  142  is on top and the reservoir  166  is on bottom. 
         [0043]    The user then begins inhaling through the delivery tube  180  or the diffuser tube  120 . As the user is inhaling, the user applies a compressive load to the blister  142  as indicated by the direction arrows L in  FIG. 4 . This may be conveniently and effectively accomplished by squeezing or depressing the blister  142  and the marginal portion  162  between the user&#39;s thumb and one or more fingers. As the user compresses the blister  142 , the pressure within the gas chamber  112  is increased, thereby applying an increasing load to the entrance membrane  152 . When a prescribed pressure is created in the gas chamber  112 , the entrance membrane  152  will burst, placing the gas chamber  112  in fluid communication with the storage volume  116 . The exit membrane  154  is substantially immediately thereafter loaded by the same pressure and bursts as well, placing the storage volume  116  in fluid communication with the passage  122 . As a result, a continuous flow path is provided from the gas chamber  112  to the delivery opening  124 . The gas  111  originally in the gas chamber  112  is displaced at high velocity through the ports  114 ,  118  and the storage volume  116  such that the gas  111  aerosolizes the medicament  5  and a plume  5 A including the medicament  5  is forced out of or expelled from the dispenser  100  as shown in  FIG. 4 . The diffuser tube  120  and/or the delivery tube  180  enable expansion and mixing of the plume and also allow the plume  5 A to slow before ultimate delivery to the user. 
         [0044]    It will be appreciated that the carrier gas  111  which aerosolizes the medicament may include some or all of the gas stored in the storage volume  116 . Moreover, dispensers according to the present invention may be configured such that the gas originally stored in the gas chamber  112  does not ultimately form a part of the plume  5 A, but rather this gas displaces a downstream quantity of gas which aerosolizes the medicament  5 . Means other than the thermoformed reservoir  166  may be employed to hold the medicament  5  in the flow path of the gas. For example, the reservoir may be separately formed from the pressurizing mechanism  110  or the diffuser tube  120 , for example. 
         [0045]    The delivery device  101  and the dispenser  100  provide a number of advantages. The dispenser  100  is cost effective to manufacture and may correspond to the cost of simply packaging single doses of the medicament  5  itself. The delivery device  101  and the dispenser  100  are easy to use. The dispenser  100  can provide a single, accurately measured dose. Because of the provision of the pressurizing mechanism  110 , the dispenser  100  does not require a high degree of inspiratory effort on the part of the user to deliver the full, prescribed dose. The dispenser  100  may be disposable, so that no cleaning or reloading is required. 
         [0046]    The preferred properties of the membranes  152 ,  154  and the configurations and dimensions of the blister  142  and the reservoir  166  will depend on the amount and characteristics of the medicament  5 , as well as the operational characteristics desired. The prescribed pressure should be high enough to create a sufficient carrier gas velocity to dispense and deaggregate the medicament  5  to thereby create a cloud of the medicament  5  which is suitable for inhalation and which can propel substantially all of the medicament  5 . A residue of the medicament  5  may remain in the reservoir  166  after application. Preferably, the amount of residue is no more than 10% of the original amount of medicament  5 . However, the prescribed pressure is preferably sufficiently low as to not require undue effort from the user to generate the prescribed pressure in the gas chamber  112 . 
         [0047]    The prescribed pressure of the dispenser  100  necessary to deliver the medicament  5  will depend on the effective burst pressure and tensile strength of one or both of the membranes  152  and  154 . The performance of the dispenser  100  may be varied by appropriately selecting and configuring the materials of the membranes to provide the effective burst pressures and tensile strengths of the membranes  152  and  154 . 
         [0048]    For some applications, it may be desirable to provide both of the membranes  152  and  154  with substantially the same effective burst pressures and/or tensile strengths. This may be accomplished by forming the membranes  152  and  154  of the same material and with the same dimensions. 
         [0049]    For some applications, it may be desirable to provide one of the membranes  152 ,  154  with a higher effective burst pressure and/or tensile strength than the other membrane  152 ,  154 . It has been found that a more complete emitted dose (i.e., less residual medicament remaining in the reservoir  166  following activation) may be achieved when one of the membranes  152 ,  154  ruptures at a pressure significantly below the prescribed pressure. In particular, it has been found that for some embodiments the residual dose is substantially reduced or effectively eliminated when the entrance membrane  152  is adapted to burst at a pressure less than the pressure required to burst the exit membrane  154 . Preferably, the entrance membrane  152  is adapted to burst at between about 20 and 80% of the pressure at which the exit membrane  154  bursts. 
         [0050]    The membranes  152 ,  154  may be adapted to burst at different pressures by appropriate selection of the relative materials, thicknesses and/or different sizes of ports  114 ,  118 . Alternatively or additionally, the following features may be used to provide differential bursting pressures. These features may be used individually or in combination. 
         [0051]    With reference to  FIG. 5 , an intermediate sheet  250  as shown therein may be substituted for the intermediate sheet  150  of the dispenser  100 . The intermediate sheet  250  includes an entrance membrane  252  and an exit membrane  254  (each indicated by dashed lines) corresponding to the membranes  152  and  154 , respectively. The intermediate sheet  250  may be formed in the same manner as the intermediate sheet  150  except that the sheet  250  is further provided with embossments  252 A and  254 A on the membranes  252  and  254  to control the break pattern of the film. The embossments can be depressions, deformations, scored regions or reduced thickness regions in the film of the sheet  250  and serve to provide preferential release portions or weakened locations. 
         [0052]    The embossments  252 A and  254 A may have different patterns (as shown) or the same pattern. One of the embossments  252 A,  254 A may be omitted. In particular, the embossment  254 A may be omitted in order to provide the membrane  252  with a lower effective burst pressure than the membrane  254 . An alternative embossment pattern includes multiple small points which, upon application of a relatively low pressure, will break to convert the selected membrane(s) into a mesh. The embossments  252 A,  254 A may be formed by any suitable means, for example, by mechanical and/or heat stamping. 
         [0053]    With reference to  FIG. 6 , a dispenser  300  according to a further embodiment is shown therein. The dispenser  300  includes upper and lower sheets  340  and  360  corresponding to the upper and lower sheets  140  and  160 , respectively, and can be constructed in the same manner as the dispenser  100  except that the intermediate sheet  150  is replaced with intermediate sheets  350 A and  350 B. The sheet  350 A includes the entrance membrane  352  (indicated by dashed lines) and the sheet  350 B includes the exit membrane  354  (indicated by dashed lines). The sheets  350 A,  350 B are formed of oriented films. As used herein, “oriented film” means a film which is drawn in the direction of flow during or after extrusion. Preferably, the sheets  350 A,  350 B are formed of uniaxially oriented films. 
         [0054]    Preferably, the films of the sheets  350 A,  350 B are oriented at different angles and, more preferably, at an angle of about 90 degrees with respect to one another. Most preferably, the film of the sheet  350 A (and, thus, the film of the entrance membrane  352 ) is oriented to tear along an axis P substantially parallel to the flow path and the film of the sheet  350 B (and, thus, the film of the exit membrane  354 ) is oriented to tear along an axis R substantially perpendicular to the flow path. 
         [0055]    With reference to  FIGS. 7 and 8 , a dispenser  400  according to a further embodiment of the present invention is shown therein. The dispenser  400  corresponds to the dispenser  100  except that the dispenser  400  is further provided with an end cap assembly  490 . The end cap assembly  490  includes a cap  492  that is removably mounted on the diffuser tube  420  as shown in  FIG. 7 . A connector string  494  is secured to the cap  492 , extends through the passage  422 , and is secured to the exit membrane  454 . 
         [0056]    In use, the user first pulls the cap  492  away from the diffuser tube  420 , thereby tearing and/or pulling a portion or all of the exit membrane  454  away as shown in  FIG. 8 . In this manner, the port  418  is partially or fully opened at a desired dispensing time. The user may then actuate the dispenser  400  in the manner described above with regard to the dispenser  100 . 
         [0057]    With reference to  FIG. 9 , a dispenser  500  according to further embodiments of the present invention is shown therein. The dispenser  500  corresponds to the dispenser  100  except as follows. A piercing member  553  can be molded into or otherwise secured to the lower sheet  560  (e.g., prior to heat sealing the upper, lower and intermediate sheets). The piercing member  553  extends into the storage volume  116  below the entrance membrane  552 . 
         [0058]    When the blister  542  is depressed, the pressure therein causes the entrance membrane  552  to deform or bulge downwardly into contact with the piercing member  553 . In this manner, the membrane  552  may be pre-pierced or burst at a pressure lower than the pressure required to burst the exit membrane  554 . 
         [0059]    With reference to  FIG. 10 , a dispenser  600  according to further embodiments of the present invention is shown therein in a partially actuated position. The dispenser  600  corresponds to the dispenser  100  except as follows. A piercing member  653  is molded into or otherwise secured to the upper sheet  640  and, more particularly, into the blister  642 . Prior to actuation of the pressurizing mechanism  610 , the piercing member  653  extends downwardly into the gas chamber  612  and is positioned suspended above the entrance membrane  652 . 
         [0060]    When the blister  642  is depressed, the piercing member  653  is displaced and moves to contact the entrance membrane  652 . In this manner, the membrane  652  may be pre-pierced or burst at a pressure lower than the pressure required to burst the exit membrane  654 . 
         [0061]    With reference to  FIG. 11 , a dispenser  700  according to further embodiments is shown therein in a partially actuated position. The dispenser  700  corresponds to the dispenser  100  except as follows. The stiffness, elasticity and other appropriate characteristics of the upper sheet  740 , the lower sheet  760  and the intermediate sheet  750  are selected such that, as the blister  742  is depressed in a direction M, the portions of the several sheets  740 ,  750 ,  760  upstream of the entrance port  714  (collectively, the dispenser portion  703 ) stretch laterally in the direction N relative to the portions of the sheets  740 ,  750 ,  760  downstream of the entrance port  714  (collectively, the dispenser portion  705 ). This stretching increases the length E of the port along the direction N (i.e., substantially along the length of the flow path) and thereby distorts the entrance membrane  752 . Such distortion creates non-uniformity in the entrance membrane  752  and resultant stress concentrations. In this manner, the entrance membrane  752  may be burst at a pressure lower than the pressure required to burst the exit membrane  754 . 
         [0062]    With reference to  FIGS. 12 and 13 , a dispenser  800  according to further embodiments of the present invention is shown therein. The dispenser  800  has an upper sheet  840 , an intermediate sheet  850  and a lower sheet  860  corresponding to the sheets  140 ,  150  and  160 , respectively, except as follows. 
         [0063]    The upper sheet  840  and the lower sheet  860  are integrally formed as a clam shell member  810  and are pivotably joined by hinge portions  812 . Cone shaped diffuser channels  844 A and  844 B are formed in the sheets  840  and  860 , respectively. To assemble the dispenser  800 , the sheets  840 ,  860  are folded or pivoted about the hinges  812  with the sheet  850  positioned therebetween. The channels  844 A,  844 B combine to form an enlarged conical diffuser tube  820 . Optionally, the channel  844 B may be replaced with a planar portion as is the dispenser  100 . 
         [0064]    The dispenser  800  has a generally accordion or bellows shaped blister  842 . The blister  842  has generally vertically extending ring shaped walls  842 A and ring shaped, rounded connecting walls  842 B. The walls  842 A are preferably substantially concentric with each other and with the walls  842 B. The blister  842  is tapered such that the diameters of the walls  842 A,  842 B decrease incrementally toward the upper end of the blister  842 . 
         [0065]    When the blister  842  is depressed, the walls  842  tend to guide the blister  842  in a vertical direction V which is preferably collinear with the common central axis of the walls  842 A,  842 B. The rounded walls  842 B allow the blister  842  to collapse easily against the underlying segments. The telescoping shape of the blister  842  helps to prevent roll-over of the blister as it is being depressed. 
         [0066]    With reference to  FIGS. 14 and 15 , a delivery device  901  according to further embodiments of the present invention is shown therein. The delivery device  901  includes a delivery tube  980  and a dispenser  900  corresponding to the dispenser  100 . The delivery tube  980  is configured and formed of a suitable material such that the delivery tube  980  is foldable. Suitable materials may include polystyrene, polyvinyl chloride (PVC), polypropylene, polyethylene, polyester or ABS. The delivery tube  980  may be maintained in a folded position, as shown in  FIG. 14 , such that portions  986 A and  986 B of the delivery tube  980  are joined along a fold  981 . This position may be particularly advantageous for storing the delivery device  901 . When the user wishes to administer a dose from the dispenser  900 , the user may unfold the portion  986 B about the fold  981  to extend the delivery tube  980  in the delivery position as shown in  FIG. 15 . 
         [0067]    With reference to  FIGS. 16 and 17 , a delivery device  1001  according to further embodiments of the present invention is shown therein. The delivery device  1001  includes a dispenser  1000  corresponding to the dispenser  100 . The delivery device  1001  further includes a delivery tube  1080 . The delivery tube  1080  includes a plurality of telescoping segments  1086 A,  1086 B,  1086 C. For storage, the delivery tube  1080  may be slidably nested or compressed as shown in  FIG. 17 . The delivery tube  1080  may thereafter be re-extended as shown in  FIG. 16  for use. 
         [0068]    With reference to  FIG. 18 , a delivery device  1101  according to further embodiments of the present invention is shown therein. The delivery device  1101  includes a dispenser  1100  corresponding to the dispenser  100 . The delivery device  1101  further includes a delivery tube  1180 . The delivery tube  1180  corresponds to the delivery tube  180  except that a plurality of baffles  1188 A and  1188 B are secured to the interior surface  1181  of the delivery tube  1180  and extend radially inwardly therefrom. The baffles  1188 A,  1188 B are preferably integrally molded into the delivery tube  1180 . The baffles  1188 A and the baffles  1188 B extend from opposing sides of the delivery tube  1180  and are arranged in a sequentially alternating fashion. The baffles  1188 A,  1188 B may serve to slow the plume of medicament from the dispenser  1100 . The baffles  1188 A,  1188 B may also serve to deaggregate the medicament and also to induce additional turbulence in the carrier gas stream to aid in mixing of the medicament with the carrier gas stream. 
         [0069]    With reference to  FIG. 19 , a delivery device  1201  according to further embodiments of the present invention is shown therein. The delivery device  1201  includes a dispenser  1200  corresponding to the dispenser  100 . The delivery device  1201  further includes a delivery tube  1280 . A helical rib  1287  is secured to and extends radially inwardly from the interior surface  1281  of the delivery tube  1280 . The rib can be integrally molded with the delivery tube  1280 . The helical rib  1287  extends down at least a portion of the length of the interior wall of the delivery tube  1280 . Preferably, the rib  1287  has a radially extending height of between about ⅕ and ⅘ of the exit tube diameter. The helical rib  1287  may serve the functions discussed above with regard to the baffles  1188 A,  1188 B. 
         [0070]    With reference to  FIG. 20 , a delivery device  1301  according to further embodiments of the present invention is shown therein. The delivery device  1301  includes a dispenser  1300  corresponding to the dispenser  100 , for example. The delivery device  1301  further includes a delivery tube  1380  corresponding to the delivery tube  180  except as follows. A mesh or screen  1389  is positioned in and secured to the interior surface  1381  of the delivery tube  1380 . Preferably, the screen  1389  extends fully across the width of the delivery tube  1380 . The preferred mesh size of the screen  1389  will depend on the optimum particle size of the powder to be delivered. The screen  1389  is preferably formed of a plastic material. The screen  1389  may serve the functions discussed above with regard to the baffles  1188 A,  1188 B. 
         [0071]    As a further alternative, baffles corresponding to the baffles  1188 A,  1188 B may be secured to and extend radially inwardly from the interior wall or the delivery opening  124  of the diffuser tube  120 , for example. Similarly, a helical rib corresponding to the helical rib  1287  may be provided in the diffuser tube  120 , for example. Also, as a further alternative, a screen corresponding to the screen  1389  may be mounted in the diffuser tube  120  or the port  124 . 
         [0072]    The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the claims. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the appended claims. The invention is defined by the following claims, with equivalents of the claims to be included therein.