Abstract:
A dry powder inhaler for delivering medicament to a patient includes a housing defining a chamber for receiving a dose of powdered medicament, an inhalation port in fluid communication with the chamber, at least one airflow inlet providing fluid communication between the chamber and an exterior of the housing, and an aeroelastic element in the chamber and associated with a dose of powdered medicament. A tensioning assembly is configured to apply a first amount of tension to the aeroelastic element such that the aeroelastic element is capable of vibrating in response to airflow through the chamber so as to aerosolize the dose of powdered medicament.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of U.S. application Ser. No. 11/713,180, entitled “Dry Powder Inhaler with Aeroelastic Dispersion Mechanism,” filed on Mar. 2, 2007, pending, which claims the benefit of priority of U.S. provisional application No. 60/778,878, entitled “Dry Powder Inhaler with Aeroelastic Dispersion Mechanism,” filed on Mar. 3, 2006, the contents of both of which are incorporated herein by reference in their entirety. 
    
    
     TECHNICAL FIELD 
     The present invention is directed generally to inhalers, for example, dry powder inhalers, and methods of delivering a medicament to a patient. More particularly, the present invention is directed to dry powder inhalers having an aeroelastic dispersion mechanism. 
     BACKGROUND 
     Dry powder inhalers (“DPIs”) represent a promising alternative to pressurized meted dose inhaler (“pMDI”) devices for delivering drug aerosols without using CFC propellants. See generally, Crowder et al., 2001: an Odyssey in Inhaler Formulation and Design, Pharmaceutical Technology, pp. 99-113, July 2001; and Peart et al., New Developments in Dry Powder Inhaler Technology, American Pharmaceutical Review, Vol. 4, n,3, pp. 37-45 (2001). Martonen et al. 2005 Respiratory Care, Smyth and Hickey American Journal of Drug Delivery, 2005. 
     Typically, the DPIs are configured to deliver a powdered drug or drug mixture that includes an excipient and/or other ingredients. Conventionally, many DPIs have operated passively, relying on the inspiratory effort of the patient to dispense the drug provided by the powder. Unfortunately, this passive operation can lead to poor dosing uniformity since inspiratory capabilities can vary from patient to patient, and sometimes even use-to-use by the same patient, particularly if the patient is undergoing an asthmatic attack or respiratory-type ailment which tends to close the airway. 
     Generally described, known single and multiple dose DPI devices use: (a) individual pre-measured doses, such as capsules containing the drug, which can be inserted into the device prior to dispensing; or (b) bulk powder reservoirs which are configured to administer successive quantities of the drug to the patient via a dispensing chamber which dispenses the proper dose. See generally, Prime et al., Review of Dry Powder Inhaler&#39;s, 26 Adv. Drug Delivery Rev., pp. 51-58 (1997); and Hickey et al., A New Millennium for Inhaler Technology, 21 Pharm. Tech., n. 6, pp. 116-125 (1997). 
     In operation, DPI devices desire to administer a uniform aerosol dispersion amount in a desired physical form (such as a particulate size) of the dry powder into a patient&#39;s airway and direct it to a desired deposit site. If the patient is unable to provide sufficient respiratory effort, the extent of drug penetration, especially to the lower portion of the airway, may be impeded. This may result in premature deposit of the powder in the patient&#39;s mouth or throat. 
     A number of obstacles can undesirably impact the performance of the DPI. For example, the small size of the inhalable particles in the dry powder drug mixture can subject them to forces of agglomeration and/or cohesion (i.e., certain types of dry powders are susceptible to agglomeration, which is typically caused by particles of the drug adhering together), which can result in poor flow and non-uniform dispersion. In addition, as noted above, many dry powder formulations employ larger excipient particles to promote flow properties of the drug. However, separation of the drug from the excipient, as well as the presence of agglomeration, can require additional inspiratory effort, which, again, can impact the stable dispersion of the powder within the air stream of the patient. Unstable dispersions may inhibit the drug from reaching its preferred deposit/destination site and can prematurely deposit undue amounts of the drug elsewhere. 
     A number of different inhalation devices have been designed to attempt to resolve problems attendant with conventional passive inhalers. For example, U.S. Pat. No. 5,655,523 discloses and claims a dry powder inhalation device which has a deagglormeration-aerosolization plunger rod or biased hammer and solenoid. U.S. Pat. No. 3,948,264 discloses the use of a battery-powered solenoid buzzer to vibrate the capsule to effectuate the efficient release of the powder contained therein. Those devices are based on the proposition that the release of the dry powder can be effectively facilitated by the use of energy input independent of patient respiratory effort. 
     U.S. Pat. No. 5,533,502 to Piper discloses and claims a powder inhaler using patient inspiratory efforts for generating a respirable aerosol. The Piper invention also includes a cartridge capable of rotating, holding the depressed wells or blisters defining the medicament holding receptacles. A spring-loaded carriage compresses the blister against conduits with sharp edges that puncture the blister to release the medication that is then entrained in air drawn in from the air inlet conduit so that aerosolized medication is emitted from the aerosol outlet conduit. 
     Crowder et al. describe a dry powder inhaler in U.S. Pat. No. 6,889,690 comprising a piezoelectric polymer packaging in which the powder for aerosolization is simulated using non-linear signals determined a priori for specific powders. 
     In recent years, dry powder inhalers (DPIs) have gained widespread use, particularly in the United States. Currently, the DPI market is estimated to be worth in excess of $4 billion. Dry powder inhalers have the added advantages of a wide range of doses that can be delivered, excellent stability of drugs in powder form (no refrigeration), ease of maintaining sterility, non-ozone depletion, and they require no press-and-breathe coordination. 
     There is great potential for delivering a number of therapeutic compounds via the lungs (see, for example, Martonen T., Smyth H D C, Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder Inhaler Performance and Lung Deposition”: Respiratory Care. 2005, 50(9); and Smyth H D C, Hickey, A J, “Carriers in Drug Powder Delivery: Implications for Inhalation System Design,” American Journal of Drug Delivery, 2005, 3(2), 117-132). In the search for non-invasive delivery of biologics (which currently must be injected), it was realized that the large highly absorptive surface area of the lung with low metabolic drug degradation, could be used for systemic delivery of proteins such as insulin. The administration of small molecular weight drugs previously administered by injection is currently under investigation via the inhalation route either to provide non-invasive rapid onset of action, or to improve the therapeutic ratio for drugs acting in the lung (e.g. lung cancer). 
     Gene therapy of pulmonary disease is still in its infancy but could provide valuable solutions to currently unmet medical needs. The recognition that the airways may provide a real opportunity for delivering biotech therapeutics in a non-invasive way was recently achieved with Exubera™, an inhaled insulin product. This product has obtained a recommendation for approval by US Food and Drug Administration and will lead to expanded opportunities for other biologics to be administered via the airways. 
     Key to all inhalation dosage forms is the need to maximize the “respirable dose” (particles with aerodynamic diameters &lt;5.0 μm that deposit in the lung) of a therapeutic agent. However, both propellant-based inhalers and current DPI systems only achieve lung deposition efficiencies of less than 20% of the delivered dose. The primary reason why powder systems have limited efficiency is the difficult balancing of particle size (particles under 5 μm diameter) and strong inter-particulate forces that prevent deaggregation of powders (strong cohesive forces begin to dominate at particle sizes &lt;10 μm) (Smyth H D C., Hickey, A J., “Carriers in Drug Powder Delivery: Implications for inhalation System Design,” American Journal of Drug Delivery, 2005, 3(2), 117-132). Thus, DPIs require considerable inspiratory effort to draw the powder formulation from the device to generate aerosols for efficient lung deposition (see  FIG. 1  for an illustration of typical mechanism of powder dispersion for DPIs). Many patients, particularly asthmatic patients, children, and elderly patients, which are important patient groups for respiratory disease, are not capable of such effort. In most DPIs, approximately 60 L/min of airflow is required to effectively deaggregate the fine cohesive powder. All currently available DPIs suffer from this potential drawback. 
     Multiple studies have shown that the dose emitted from dry powder inhalers (DPI) is dependent on air flow rates (see Martonen T., Smyth H D C, Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder Inhaler Performance and Lung Deposition”: Respiratory Care. 2005, 50(9)). Increasing air-flow increases drug dispersion due to increases in drag forces of the fluid acting on the particle located in the flow. The Turbuhaler® device (a common DPI), is not suitable for children because of the low flow achieved by this patient group (see Martonen T., Smyth H D C, Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder Inhaler Performance and Lung Deposition”: Respiratory Care. 2005, 50(9)). 
     Considerable intra-patient variability of inhalation rates has been found when patients inhale through two leading DPI devices. That inherent variability has prompted several companies to evaluate ways of providing energy in the inhaler (i.e. “active” DPIs). Currently, there is no active DPI commercially available. The active inhalers under investigation include technologies that use compressed air, piezoelectric actuators, and electric motors. The designs of those inhalers are very complex and utilize many moving parts and components. The complexity of those devices presents several major drawbacks including high cost, component failure risk, complex manufacturing procedures, expensive quality control, and difficulty in meeting specifications for regulatory approval and release (Food and Drug Administration). 
     Alternatively, powder technology provides potential solutions for flow rate dependence of DPIs. For example, hollow porous microparticles having a geometric size of 5-30 μm, but aerodynamic sizes of 1-5 μm require less power for dispersion than small particles of the same mass. This may lead to flow independent drug dispersion but is likely to be limited to a few types of drugs with relevant physicochemical properties. 
     Thus there are several problems associated with current dry powder inhaler systems including the most problematic issue: the dose a patient receives is highly dependent on the flow rate the patient can draw through the passive-dispersion device. Several patents describing potential solutions to this problem employ an external energy source to assist in the dispersion of powders and remove this dosing dependence on patient inhalation characteristics. Only one of these devices has made it to market or been approved by regulatory agencies such as the U.S. Food and Drug Administration. Even upon approval, it is likely that these complex devices will have significant costs of manufacture and quality control, which could have a significant impact on the costs of drugs to patients. 
     The present disclosure describes exemplary dry powder inhalers and associated single or multi-dose packaging, which holds the compound to be delivered for inhalation as a dry powder. These dry powder inhalers bridge the gap between passive devices and active devices. The inhalers are passive devices that operate using the energy generated by the patient inspiratory flow inhalation maneuver. However, the energy generated by airflow within the devices is focused on the powder by using oscillations induced by airflow across an aeroelastic element. In this way the inhalers can be “tuned” to disperse the powder most efficiently by adjusting the resonance frequencies of the elastic element to match the physicochemical properties of the powder. In addition, the airflow rate required to generate the appropriate oscillations within the device is minimized because some of the energy used to create the vibrations in the elastic element is pre-stored in the element in the form of elastic tension (potential energy). Inhaler performance may be tailored to the lung function of individual patients by modulating the elastic tension. Thus, even patients with poor lung function and those who have minimal capacity to generate airflow during inspiration will able to attain the flow rate required to induce oscillations in the elastic element. 
     SUMMARY OF THE INVENTION 
     An exemplary embodiment of the invention comprises a dry powder inhaler with an integrated assisted dispersion system that is adjustable according to the patients&#39; inspiratory capabilities and the adhesive/cohesive nature of the powder. The inhaler comprises an aeroelastic element that flutters or oscillates in response to airflow through the inhaler. The aeroelastic element provides concentrated energy of the airflow driven by the patient into the powder to be dispersed. The aeroelastic element is preferably a thin elastic membrane held under tension that reaches optimal vibrational response at low flow rates drawn through the inhaler by the patient. The aeroelastic element is preferably adjustable according to the patient&#39;s inspiratory capabilities and the adhesive/cohesive forces within the powder for dispersal. 
     According to various aspects of the disclosure, a dry powder inhaler for delivering medicament to a patient includes a housing defining a chamber for receiving a dose of powdered medicament, an inhalation port in fluid communication with the chamber, at least one airflow inlet providing fluid communication between the chamber and an exterior of the housing, and an aeroelastic element in the chamber and associated with a dose of powdered medicament. A tensioning assembly is configured to apply a first amount of tension to the aeroelastic element such that the aeroelastic element is capable of vibrating in response to airflow through the chamber so as to aerosolize the dose of powdered medicament. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates airflow across an aeroelastic element in accordance with various aspects of the disclosure. 
         FIG. 2  illustrates airflow past an airflow modifier and across an aeroelastic element in accordance with various aspects of the disclosure. 
         FIG. 3A  is a schematic representation of a top cross-sectional view of an exemplary inhaler in accordance with various aspects of the disclosure. 
         FIG. 3B  is a schematic representation of an end cross-sectional view of an exemplary inhaler in accordance with various aspects of the disclosure. 
         FIG. 4  is a schematic representation of first and second rollers loaded with the aeroelastic membrane with axles in the center of the rollers in accordance with various aspects of the disclosure. 
         FIG. 5  is representation of an exemplary dosing applicator in accordance with various aspects of the disclosure. 
         FIG. 6  is a representation of another exemplary dosing applicator in accordance with various aspects of the disclosure. 
         FIGS. 7A-7C  are representations of an exemplary aeroelastic membrane and its relation to exemplary base clamps, upper clamps, and tensioning rods in accordance with various aspects of the disclosure. 
         FIG. 8  is a representation of an exemplary dispensing mechanism in accordance with various aspects of the disclosure. 
         FIG. 9  is a representation of an alternative exemplary dispensing mechanism in accordance with various aspects of the disclosure. 
         FIG. 10  is a representation of an alternative exemplary dispensing mechanism in accordance with various aspects of the disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     An exemplary embodiment of a dry powder inhaler  100  is illustrated in  FIGS. 3A and 3B . According to various aspects of the disclosure, the dry powder inhaler  100  may comprise a casing  102  having an outer wall  104  and two inner walls  106 ,  108 . The inner walls  106 ,  108  may extend in a first direction from a first inner surface  112  of the outer wall  104  toward a second inner surface  114  of the outer wall  104 . The inner walls  106 ,  108  may also extend in a second direction from a proximal end  116  of the casing  102  to a distal end  118  of the casing  102 . Thus, according to various aspects, the outer wall  104  and inner walls  106 ,  108  may cooperate to define three chambers in the casing  102 . 
     According to some aspects, the three chambers may include a middle chamber  122  and two side chambers  124 ,  126  located on opposite sides of the middle chamber  122  relative to one another. The side chambers may comprise a first side chamber  124  located to a first side of the middle chamber  122  and a second side chamber  126  located to a second side of the middle chamber  122 . 
     In accordance with various aspects, the distal end  118  of the casing  102  may include one or more airflow inlets  128  providing fluid communication between the middle chamber  122  and ambient air outside the casing  102 . The proximal end  116  of the casing  102  may include a mouthpiece  130 . The mouthpiece  130  may a separate structure affixed to the outer wall  104  of the casing  102 , or the mouthpiece  130  and casing  102  may comprise a single piece of unitary construction. The mouthpiece  130  may include an opening  132  providing fluid communication between the middle chamber  122  and the outside of the casing  102 . The opening  132  may be shaped as an oval, a circle, a triangle, or any other desired shape. The mouthpiece  130  may have a shape that facilitates pursing of a patient&#39;s lips over the mouthpiece  130  and creating a seal between the lips and the mouthpiece  130 . 
     The inhaler  100  may include a nozzle  134  between the middle chamber  122  and the opening  132 . According to various aspects, the nozzle  134  may extend from the opening  132 , through the mouthpiece  130 , and into the middle chamber  122 . In some aspects, the nozzle  134  may comprise at least one helical tube  136  through which air and powder can be inhaled. The tube  136  can be configured to increase the turbulence in the air that flows through the nozzle  134 . 
     An aeroelastic element  140  may extend across a center region  142  of the middle chamber  122  between the inner walls  106 ,  108 . The aeroelastic element  140  may include one or more doses of a medicament  141 , for example, doses of powdered medicament, and the center region  142  may comprise a region for dispensing a dose of medicament into airflow through the inhaler  100 . According to some aspects, the aeroeslastic element  140  may comprise a membrane  144 , for example, a thin elastic membrane, wound between two spools  146 ,  148 . An unused end of the membrane  144  may be wound on a first spool  146 , and a used end of the membrane  144  may be wound on a second spool  148 . The first spool  146  may be disposed about a first axle  147 , and the second spool  148  may be disposed about a second axle  149 . The first spool  146  may be in the first side chamber  124 , and the second spool  148  may be in the second side chamber  126 . In such an embodiment, the membrane  144  extends through a slot  150  in the inner wall  106 , across the center region  142 , and through a slot  152  in the inner wall  108 . In accordance with some aspects, the aeroelastic element  140  may comprise a membrane, a film, a reed, a sheet, a panel, or a blade. The aeroelastic element may be manufactured of materials comprising polymers, thin metals, polymer-coated metals, and/or metal-coated polymers. 
     According to various aspects, the inhaler  100  may include two base clamps  154 ,  156  fixedly attached to a first inner surface  112  of the casing  102 . According to some aspects, the base clamps  154 ,  156  may be in the middle chamber  122 . A first of the base clamps  154  may be between the center region  142  and the first inner wall  106 , and the second of the base clamps  156  may be between the center region  142  and the second inner wall  108 . The aeroelastic element  140  may rest on the base clamps  154 ,  156 . The inhaler  100  may include two upper clamps  158 ,  160  in the middle chamber  122  associated with the two base clamps  154 ,  156 . For example, a first upper clamp  158  may be on an opposite side of the aeroelastic element  140  relative to the first base clamp  154  and configured to descend atop the first base clamp  154  to sandwich the aeroelastic element therebetween. Similarly, the second upper clamp  160  may be on an opposite side of the aeroelastic element  140  relative to the second base clamp  156  and configured to descend atop the second base clamp  156  to sandwich the aeroelastic element therebetween. The upper clamps  158 ,  160  and base clamps  154 ,  156  may hold the aeroelastic element  140  in place across the center region  142  with a desired amount of tension. The desired amount of tension may be determined based on a user&#39;s inhalation strength. It should be appreciated that in some aspects, the upper clamps may be fixedly attached to the second inner surface  114  of the casing  102 , and the base clamps may be configured to ascend toward the upper clamps to sandwich the aeroelastic element therebetween. 
     In an alternative embodiment (not shown), a first of the base clamps  154  may be in the first side chamber  124  between the first spool  146  and the first wall  106 , and the second of the base clamps  156  may be in the second side chamber  126  between the second spool  148  and the second wall  108 . 
     The inhaler  100  may include an advancement member  162  extending outward of the casing  102 . The advancement member  162  may comprise, for example, a lever, a dial, or the like. The advancement member  162  may be mechanically coupled to the first and second upper clamps  158 ,  160  via, for example, a crank  164  or other known linkage. The advancement member  162  and crank  164  are structured and arranged such that when the advancement member  162  is actuated by a user, the crank  164  is caused to move the upper clamps  158 ,  160  in a direction away from the base clamps  154 ,  156 . Actuation of the advancement member  162  may also cause the second axle  149  to turn in a manner that increases the used end of the aeroelastic element  140  wound thereon. 
     According to some exemplary aspects, as shown in  FIGS. 7A-7C , the inhaler  100  may include one or more tensioning rods  166 ,  168  configured to increase the tension of the aeroelastic element  140  beyond the tension applied by the base clamps  154 ,  156  and upper clamps  158 ,  160 . The tensioning rods  166 ,  168  are between the first and second upper clamps  158 ,  160 . The tensioning rods  166 ,  168  may be mechanically coupled to the crank  164  such that actuation of the advancement member  162  causes the tensioning rods  166 ,  168  to move in a direction away from the aeroelastic element  140 . When the advancement member  162  is released or unactuated, the tensioning rods  166 ,  168  return to a position that applies a desired amount of tension to the aeroelastic element  140 . It should be appreciated that in some aspects, one or more tension controllers  157 ,  159  ( FIG. 4 ) may be attached to one or both of the spool axles  147 ,  149 , thus allowing the tension of the aeroelastic element  140  to be manually fixed and maintained across the spool axles  147 ,  149  and obviating the need for tensioning rods. In any design, the amount tension applied by the clamps, tensioning rods, and/or tension controllers can be determined based on inhalation strength of a user. 
     Referring again to  FIG. 3B , in various aspects, the second axle  149  associated with the second spool  148  may comprise a concentric spring  170 , which is mechanically coupled to the advancement member  162  so that actuation of the advancement member  162  results in the aeroelastic element  140  being transferred from the first spool  138  to the second spool  148  as the spring-loaded axle  149  is activated. The inhaler  100  may include a roller  172  ( FIG. 5 ) adjacent to the first spool  146  and engaging the aeroelastic element  140 , thereby resulting in additional tension in the aeroelastic element. 
     According to some aspects, for example, inhalers having an aeroelastic element with multiple doses of medicament, a dose counter  174  may be mechanically coupled to the advancement member  162  in such a way that the dose counter  174  changes numbers by one each time the advancement member  162  is actuated. In some aspects, the dose counter  174  may be at an exterior surface of the casing  102  so as to be visible to a user. In some aspects, the dose counter  174  may be inside the casing  102 , but visible to a user via a transparent or translucent window (not shown), as would be understood by persons skilled in the art. 
     According to various aspects, as shown in  FIG. 5 , the inhaler  100  may include a powder dose applicator  176  located between the first spool  146  and the first base clamp  154 . In some aspects, the powder dose applicator  176  may include a dispensing chute  178  filled with at least one dose of powder  180 . The dispensing chute  178  may include a top end  182  and a bottom end  184 . A wheel  186  may be at the bottom end of the dispensing chute  178 . The wheel  186  may be rotatable about an axle  188 . The axle  188  may be mechanically coupled to the advancement member  162  such that the wheel  186  rotates an amount sufficient to dispense one dose of powdered medicament to the aeroelastic element. For example, the wheel  186  may include one or more notches  190  in its periphery, with the volume of each notch being sized for one dose of powdered medicament. 
     According to some aspects, the wheel shown in  FIG. 5  may be replaced with a dispensing disk  686 , as shown in  FIG. 6 . For example, the dispensing chute  178  above the aeroelastic element  140  is filled with at least one dose of powdered medicament. The dispensing disk  686  may be located between the aeroelastic element  140  and the dispensing chute  178  and may be in contact with the bottom end  184  of the chute  178 . The disk  686  may further include multiple dispensing openings  690  clustered in one section of the disk  686 , for example, a periphery of the disk  686 . The dispensing openings  690  correspond to an accurate amount of powdered medicament to be dispensed as a dose. The dispensing disk  686  rotates about an axle  688  as the advancement member  162  is actuated, thereby resulting in an accurate amount of powdered medicament falling through the dispensing openings  690  and to the aeroelastic element  140 . For example, the disk  686  may make one complete 360° rotation each time the advancement member  162  is actuated. 
     In various aspects, the inhaler  100  may include blister strip packaging attached to the two spools in place of the powder dose applicators discussed above. For example, as shown in  FIG. 8 , the blister strip packaging  801  may include at least one individual dosing cup  803 . Each cup  803  may be filled with a dose of powdered medicament and covered by a peelable top layer. The dosing cups  803  may be arranged serially along the length of the packaging strip  801 . An aeroelastic element  840  may be streteched across the center region  142  and fixedly coupled to, for example, the inner walls or any other structure capable of maintaining the element  840  fixedly stretched across the center region  142 . The strip  801  may be in proximity to the aeroelastic element  840  in the center region  142  such that the aeroelastic element  840  may act as an actuator, making contact with the blister packaging and dispersing the powder dose when the aeroelastic element begins to vibrate during inhalation by a patient. A powder dose opener  805  may be configured to remove the top peelable layer from the blister strip packaging  801  for one dose when the blister strip  801  is advanced from the first spool to the second spool. The powder dose opener may alternatively be a simple puncturing device, such as a needle, that inserts small holes in the blister strip blister cavity, making the dose ready for inhalation. 
     In some embodiments, as shown in  FIG. 9 , blister strip packaging  901  may include clusters  905  of multiple small dosing cups  903  for simultaneous multiple drug dosing, the clusters  905  may be arranged serially along the length of the blister strip  901 . The large arrows depict the direction of airflow across the blister strip and aeroelastic element. The small vertical arrows depict the vibrational motion of the aeroelastic element. In various embodiments, as shown in  FIG. 10 , the inhaler may include an aeroelastic element  1040  that may comprise, for example, an aeroelastic and deformable membrane. The element  1040  may include at least one individual dosing cup  1003  filled with a dose of powdered medicament in the form of blister strip packaging  1001 . The dosing cup  1003  may be configured to deform and raise the powder dose to the level of the surrounding element  1040 . 
     It should be appreciated that the inhaler may comprise a single powder dose such that the inhaler may be disposed of after a single use. 
     Referring again to  FIG. 5 , in some aspects, the inhaler  100  may include two rollers  192 , one above and one below the aeroelastic element  140 . The rollers  192  may be between the powder dose applicator  176  and the first base clamp  154  or between the powder dose applicator  176  and the inner wall  106 . The rollers  192  turn as the aeroelastic element  140  moves from the first spool  146  to the second spool  148  due to the frictional force applied by the aeroelastic element  140  as it is urged past the pinching rollers  192 . The rollers  192  fully engage the aeroelastic element  140  and flatten the powder deposited onto the aeroelastic element  140  and break up clumps in the powder. 
     Thus, the advancement member  162  may be capable of turning the crank to release the upper clamps and tensioner rods, advancing the dose counter, turning the wheel in the dispensing chute, advancing the spring-loaded axle in the second spool by one position to advance the aeroelastic element a predetermined distance from the first spool to the second spool, and/or moving a dose of powder medicament into the center region  142 . 
     Referring again to  FIGS. 3A and 3B , according to various aspects, the inhaler  100  may include one or more airflow modifiers  198  proximal of the one or more airflow inlets  128  and at a distal end of the center region  142 . It should be appreciated that the one or more airflow modifiers  198  may be distal of the center region  142  and/or at a distal portion within the center region  142 . In some aspects, the one or more airflow modifiers  198  may comprise multiple triangular rods extending from the first inner wall  106  to the second inner wall  108 . As air flows through the one or more airflow inlets  128  and toward the center region  142 , the one or more airflow modifiers  198  may cause vortices that allow air to pass above and below the modifiers. 
     Referring now to  FIG. 1 , airflow at velocity V over an aeroelastic element under tension is illustrated. As shown, the airflow may result in flutter or vibration of the aeroelastic element  140 . The vibration is represented by vertical arrows, and the airflow is represented by horizontal arrows.  FIG. 2  illustrates the airflow at velocity V past an airflow modifier prior to encountering an aeroelastic element  140 . As shown, the airflow modifier introduces turbulence into the airflow, thus increasing the vibration or flutter of the aeroelastic element for a given inhalation strength. 
     In operation, a method for dispensing powder by inhalation using any of the aforementioned exemplary dry powder inhaler apparatuses may begin with a patient actuating the advancement member. The patient may purse his/her lips around the mouthpiece and inhales. As the patient inhales, air is sucked into the inhaler through one or more airflow inlets at the distal end of the inhaler. The inhaled air flows over the airflow modifiers. The airflow then encounters the aeroelastic element, causing the element to vibrate or flutter and disperse a dose of powdered medicament from the element into the airflow. The combined flow of air and powder then flow into the distal end of the airflow nozzle and the mouthpiece. The combined flow of air and powder leave the mouthpiece and enter the patient&#39;s mouth and respiratory tract. The airflow modifiers and/or the helical shape of the nozzle may increase the turbulence of the airflow to better aerosolize and break up the powdered dose of medicament into smaller particles, thus maximizing the dose received by the patient and allowing the smaller particles to pass further into the respiratory tract. 
     It will be apparent to those skilled in the art that various modifications and variations can be made in the inhalers and methods of the present disclosure without departing from the scope of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.