Abstract:
The present invention provides for the integration of drug dispersion methods into a drug or medicine delivery system. The drug dispersion methods used include shear (e.g., air across a drug, with or without a gas assist), capillary flow or a venturi effect, mechanical means such as spinning, vibration, or impaction, and turbulence (e.g., using mesh screens, or restrictions in the air path). These methods of drug dispersion allow for all of the drug in the system to be released, allowing control of the dosage size. These methods also provide for drug metering, fluidization, entrainment, deaggragation and deagglomeration. The present invention also provides for the integration of a drug sealing system into the device. The drug sealing system provides a way of blocking the migration of drug from one area of the package to another. The drug seal system can also provide a method of tightly containing the drug until the package is opened, of directing airflow through the package and of managing and containing the drug during the package/device manufacturing process.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. patent application Ser. No. 11/491,004 filed Jul. 20, 2006, which claims the benefit under 35 U.S.C. 119(e) of the U.S. Provisional Applications Ser. No. 60/734,575, filed Nov. 8, 2005, Ser. No. 60/703,032 filed Jul. 27, 2005, and Ser. No. 60/700,947 filed Jul. 20, 2005, each of which is entitled “INHALATION DEVICE” and each of which is incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The present invention relates to a system for storing and delivering substances, such as medicines. The present invention is particularly useful for the administration of medicine by inhalation. 
         [0003]    Various drugs in dry powder form may be inhaled directly into the lungs through the mouth or nose. Inhalation allows the drug to bypass the digestive system and may eliminate the need for other more invasive drug application techniques, such as hypodermic injections. Direct inhalation can also allow smaller doses of a drug to be used to achieve the same desired results as the same drug taken orally. Inhalation can also help avoid certain undesirable side effects associated with taking a medicine orally or by injection. 
         [0004]    One form of delivery device that is employed for inhaling a drug is the pressurized aerosol or metered dose inhaler (MDI). MDI&#39;s are, however, not suitable for use by all patients, e.g., small children, or for the administration of all medicaments. In addition, MDI&#39;s use propellants that can cause environmental damage. A widely used alternative is the so-called dry powder inhaler in which medicament powder is dispensed from an elongate gelatin capsule by causing the capsule to rotate and/or vibrate in an airstream, releasing the medicament that is inhaled by the patient. The capsules may be pierced by a suitable puncturing mechanism to release the medicament, or the capsules may be supplied in pre-pierced form. Additional packaging that prevents loss of powder from the capsule and the ingress of moisture is often necessary. 
         [0005]    Gelatin capsules, and known drug delivery devices for inhalation, suffer from numerous disadvantages. For example, gelatin capsules are not impervious to moisture so exposure to the atmosphere can result in absorption of moisture. This may lead to agglomeration of the medicament powder particles. These problems may be particularly acute where, as is often the case, the medicament is hygroscopic. As a result, capsules must be packaged in secondary packaging such as a blister package, which significantly increases the overall bulk of the device. In addition, the secondary packaging can be unwieldy or difficult to open, particularly in an emergency situation where the medicine must be delivered as fast as possible under stressful circumstances. 
         [0006]    Another disadvantage with the gelatin capsules is that they may become brittle. In this case, the piercing operation may produce shards or fragments that can be inhaled by the patient. In addition, gelatin is a material of biological origin and therefore often contains a certain amount of microbiological organisms, leading to possible contamination of the medicament. 
         [0007]    Removal of the capsule from the secondary packaging and loading it into the device may require a degree of dexterity greater than that possessed by some patients. In addition, the motion of the elongate gelatin capsule within the device may be irregular, leading to incomplete or variable dispensing of the powdered medicament. 
         [0008]    Other dry powder inhaler systems use foil based drug storage configurations. These systems also suffer from a variety of disadvantages. Many foil-based systems require complex manufacturing and filling processes. In addition, to open these foil based systems, external puncturing mechanisms, which can cause “dead spots” of trapped medication, are normally used. 
       SUMMARY 
       [0009]    The present invention meets the foregoing objects by providing a sealed device for storing and delivering a substance, such as a medicine. The system and method for storing and delivering a medicine into an air path includes a first chamber that constrains the medicine to a particular area. Part of the first chamber defines at least one boundary of the air path. The air path is originally sealed but is capable of being opened by a first opening device that is capable of opening at least one air passage into the air path. This allows dispersion of said medicine into said air path. The system further includes a dose metering system that is integral with the first chamber. The dose metering system may be located inside the first chamber or it may be part of the wall of the first chamber. In some aspects of the invention, the dose metering system may include an air deflection system. 
         [0010]    The system may have a moisture impermeable barrier that at least partially seals the air path. The first opening device, a second opening device or a combination thereof may be used to open an air passage into the air path. Penetration of the moisture impermeable barrier, or movement of another part of the system that seals the air path provides the requisite opening. In some embodiments, the first opening device is internal to the first chamber. A preferred second opening device is a plunger which may have a cutting edge. 
         [0011]    The system may also have a second chamber interior to the first chamber. This second chamber may contain the medicine and this second chamber may be movable relative to the first chamber. For example, the second chamber may be movable from a first position to a second position by the action of a second opening device like a plunger. The second chamber may include access holes that allow dispersion of the medicine into the air path when the second chamber has moved to the second position. Preferably, the second chamber is constructed such that the access holes are blocked to prevent release of the medicine into the air path when the second chamber is in the first position but the access holes are opened when the second chamber is moved to the second position. 
         [0012]    The system may also include an obstacle that delineates at least a portion of the air path in conjunction with at least one wall of the first chamber. The obstacle may form part of a wall of the second chamber. 
         [0013]    The system may include an active method of assisting in dispersing the medicine into the air path. One active way of assisting in the dispersion is a source of active air flow to assist in dispersing the medicine into the air path. Preferred sources of active air flow are a fan and a source of compressed air. When using the active air flow source, the system may include a mixing chamber, preferably one made of a flexible material. Alternatively, the system may also include a source of vibration to assist in dispersing the medicine into the air path. The vibration source can cause the second chamber to tumble. 
         [0014]    The present invention provides for the integration of drug or medicine dispersion methods into the medicine delivery system. The dispersion methods used include shear (e.g., air across a drug, with or without a gas assist), capillary flow or a venturi effect, mechanical means such as spinning, vibration, or impaction, and turbulence (e.g., using mesh screens, or restrictions in the air path). These methods of drug dispersion allow for all of the drug in the packaging device to be released, allowing control of the dosage size. These methods also provide for drug metering, fluidization, entrainment, deaggragation and deagglomeration. 
         [0015]    The present invention also provides for the integration of a drug sealing system into the medicine delivery system. The drug sealing system provides a method of blocking the migration of drug from one area of the package to another. The drug sealing system can also provide a way of tightly containing the drug until the air path in the system is opened, of directing airflow through the package and of managing and containing drug during the manufacturing process. 
         [0016]    All of the design embodiments of the medicine delivery system can be configured for passive or active applications. In particular, variants can be made on each of the designs that use compressed air, vibration, spinning or the like to assist in dispersing the drug. The disclosed drug package can be integrated into a wide variety of inhaler configurations including a single-dose and multi-dose applications in either active or passive design format. In addition, the concepts described could also be applied to combination dose configurations and therapies. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0017]      FIGS. 1A and 1B  illustrate a basic variant of the drug or medicine delivery system of the invention having a sealed air path and a screen or mesh for drug dispersion in open and closed position; 
           [0018]      FIGS. 2A and 2B  illustrate a drug delivery system such as is shown in  FIGS. 1A and 1B  in open and closed position but with the addition of a plunger that pierces the seal and activates the internal opening mechanism. 
           [0019]      FIGS. 3A and 3B  illustrate a drug delivery system with a second chamber in an open and closed position that allows for a venturi effect to assist in drug dispersion; 
           [0020]      FIGS. 4A and 4B  illustrate a drug delivery system similar to that of  FIGS. 3A and 3B  except it includes an active air supply that assists in drug dispersion; 
           [0021]      FIGS. 5A and 5B  illustrate a drug delivery system similar to that of  FIGS. 3A and 3B  except it is designed to allow vibration to assist in drug dispersion; 
           [0022]      FIGS. 6A and 6B  illustrate a drug delivery system similar to that of  FIGS. 5A and 5B  except it includes an active vibration source to assist in drug dispersion; 
           [0023]      FIGS. 7A and 7B  illustrate a drug delivery system with a second chamber in an open and closed position that allows for tumbling or shaking of the second chamber to assist in drug dispersion; 
           [0024]      FIGS. 8A and 8B  illustrate a drug delivery system similar to that of  FIGS. 7A and 7B  except it includes an active air flow source to assist in drug dispersion; 
           [0025]      FIGS. 9A and 9B  illustrate a drug delivery system with a second chamber in an open and closed position that allows for spinning of the third chamber to assist in drug dispersion; 
           [0026]      FIGS. 10A and 10B  illustrate a drug delivery system similar to that of  FIGS. 9A and 9B  except it includes an active air flow source to assist in drug dispersion; 
           [0027]      FIGS. 11A and 11B  illustrate a drug delivery system that includes a spinning source to assist in drug dispersion; 
           [0028]      FIGS. 12A and 12B  illustrate a multidose delivery system in an open and closed position; 
           [0029]      FIGS. 13A and 13B  illustrate a simple variant of the drug delivery system using a shaped geometry to assist in dispersing the drug in the open and closed positions; and 
           [0030]      FIGS. 14A and 14B  illustrate a variant of the drug delivery system of  FIGS. 13A and 13B  with an integral opening device in addition to the shaped geometry to assist in dispersing the drug in the open and closed positions. 
       
    
    
     DETAILED DESCRIPTION 
       [0031]    The medicine storage and delivery system of the present invention provides an improved package for storing and delivering a medicine. The enhanced sealing of the device promotes improved delivery of the medicine by providing better protection of the medicine from the elements, particularly if it is in the form of a powder, and improved opening of the packaging to eliminate “dead spots.” In addition, the present invention provides active and passive variants that allow for better drug dispersion and improved delivery capabilities. 
         [0032]    The following definitions are used throughout the specification and the claims: 
         [0033]    The term “puncturing” refers to any form of opening, including piercing, perforating, peeling and tearing. 
         [0034]    The term “internal opening mechanism” or “IOM” refers to a device that is used to puncture or open at least one portion of a sealed device. The IOM can take many forms including a tube shape with an annular cutter at each end, or a sliding internal chamber with a piercing end. The internal opening mechanism can act as a structural support to minimize deformation of the drug package by an external opening device. 
         [0035]    The term “drug seal system” “DSS” refers to a component or interaction between components that provide a means of blocking the migration of drug from one area of the package to another. The drug seal system can also provide a means of tightly containing the drug until the package is opened, a means of directing airflow through the package and a means of managing and containing drug during the package/device manufacturing process. The drug sealing system can vary from a chamber to a flat cover depending on the package requirements. The DSS can also provide a cutting edge for opening the air path, and can be located inside or outside a moisture barrier. In embodiments where the DSS is located outside the moisture barrier, it could be a part of the inhaler device or a separate piece. 
         [0036]    The term “dose metering system” or “DMS” refers to a dedicated component, a specific geometry associated with a component, or the interaction between two or more components, that is designed to facilitate drug fluidization and dispersion along the air path through the drug package. The DMS can be integrated into the internal opening mechanism, the moisture barrier, the air path, the drug sealing system or in combination with any of these components, or can be a stand alone component. The DMS can be activated by actuation of the IOM or DSS, can have a stationary geometry or be a movable component, can be passive or active, and can utilize aerodynamics, compressed air, vibration or centrifugal force. 
         [0037]    The term “external plunger” or “plunger” refers to a movable component that is designed an air passage into the air path to open. The external plunger can be designed to pierce the seal of the air path from the outside by means of a cutting protuberance or can be designed to press the moisture barrier against an internal cutting protuberance located on the IOM, DSS, DMS or combination of these. The external plunger minimizes the space required to open the package, can activate the simultaneous opening of the air path by the IOM and drug sealing system (if applicable) and DMS (if applicable), and can act as a drug seal in some embodiments. Furthermore, the external plunger can be designed to provide the air inlet into the drug package, through the plunger. Air channels integrated into the plunger can direct airflow in a manner critical to emptying drug from the package. 
         [0038]    The term “active” refers to use of an external mechanism or force in addition to the patient&#39;s respiration. 
         [0039]    The term “passive” refers to the use of the patient&#39;s respiration alone. 
         [0040]    The term “chamber” refers to an area of the system that includes a portion that encloses a specific area. Chambers can be a number of shapes depending on the desired fluid dynamic interaction with the airflow. Chamber walls can include channels that direct or divert airflow through or around the inside or outside of the chamber. Chambers can vary in shape from one portion of the chamber to another. Chambers can be movable or stationary. 
         [0041]    The term “reservoir” is a storage area for holding drug. Reservoirs can have opening(s) that include a shaped geometry that is optimized to direct or divert the flow of air from the air path into, around or through the reservoir. The shaped geometry can also facilitate powder fluidization, entrainment, dispersion and deaggregation/deagglomeration. Openings can be symmetrical or asymmetrical and oriented perpendicular, parallel or at some angle to the airflow. 
         [0042]    The invention is best described in conjunction with the following Figures. 
         [0043]      FIGS. 1A and 1B  show a basic variant of the drug delivery system of the invention.  FIG. 1A  shows the device in the closed position and  FIG. 1B  shows it in the open position. The drug delivery system includes moisture barrier  101 , internal opening mechanism  102 , outlet ring  103  (with integral drug sealing system), and dose metering system  104 . 
         [0044]    Moisture barrier  101  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  101  when attached together. Furthermore, the top and bottom layers have a formed step  108  that interfaces with outlet ring  103 . Internal opening mechanism  102  resides within moisture barrier  101  and is integral with first chamber  111 . The drug dose resides inside first chamber  111 . 
         [0045]    First chamber  111  has an air inlet opening and an air outlet opening, which are in close proximity with the moisture barrier  101  when the package is assembled. First cutting edge  106  and second cutting edge  107  are located proximate to first and second openings in first chamber  111 . The dose sealing system consists of outlet ring  103  and base  105 . The dose sealing system provides an annular pressure creating a tight seal  112  between internal opening mechanism  102  and moisture barrier  101  at both of the first chamber  111  openings. 
         [0046]    A dose metering system in the form of a mesh screen  104  is integrated into the first chamber  111 . 
         [0047]    To open the package and release the drug, pressure is applied to base  105 , causing base  105  to move toward outer ring  103 . This action applies pressure on the formed steps  108  in moisture barrier  101 , causing moisture barrier  101  to slide against internal opening mechanism  102 , which pierces moisture barrier at the first and second cutting edge. This opens an air path  109  through first chamber  111 . The foil layers of moisture barrier  101  deform  110  to allow the relative movement of base  105  and outer ring  103 . 
         [0048]    Air can be drawn through the open first chamber  111 , entraining drug into the air stream. Dose metering system  104  prevents the powder from leaving the package as one large clump and helps fluidize the dose. 
         [0049]      FIG. 2  illustrates a drug delivery device substantially similar to that of  FIG. 1  except that the inlet side of the moisture barrier is pierced with an external piercing device integrated into a plunger. 
         [0050]    Moisture barrier  201  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  201  when attached together. Furthermore, the top layer has a formed step  208  that interfaces with outlet ring  203 . Internal opening mechanism  202  resides within moisture barrier  201  and is integral with first chamber  209 . The drug dose resides inside first chamber  209 . 
         [0051]    First chamber  209  has multiple openings including air inlet  212  and outlet  211 , which are in close proximity with the moisture barrier  201  when the package is assembled. There is a first cutting edge  206  at the outlet opening  211  in first chamber  209  and a second cutting edge  207  integrated into a protuberance on the plunger  205 . 
         [0052]    The dose sealing system consists of the outlet ring  203 , which provides annular pressure creating a tight seal  215  between internal opening mechanism  202  and moisture barrier  201  at first chamber outlet opening  211 . In this embodiment, the dose sealing system includes external annular ring (not shown) or interference fit  216  between moisture barrier  201  and internal opening mechanism  202 . 
         [0053]    Integrated into first chamber  209  is a dose metering system in the form of a screen  204 . 
         [0054]    To open the package, plunger  205  is moved toward outlet ring  203 , which causes the plunger protuberance  207  to pierce moisture barrier  201  at inlet opening  212  proximate to first chamber  209 . The plunger protuberance moves into first chamber  209  until the plunger shoulder  213  contacts the internal opening mechanism  202  at the inlet opening edge  214 . As plunger  205  continues to move towards outlet ring  203 , the internal opening mechanism slides against moisture barrier  201 , causing first cutting edge  206  to protrude through moisture barrier  201  at outlet opening  211 . Moisture bather  201  deforms  210  to allow the relative movement of plunger  205  and outlet ring  203 . 
         [0055]    Air can be drawn through the open first chamber  209 , possibly through plunger  205 , entraining drug into the air stream. Drug metering system  204  prevents the drug from leaving the package as one large clump and helps fluidize the dose. 
         [0056]    In alternate configurations, the drug metering system may be outside of the first chamber, or may not be present in the package. 
         [0057]    The drug delivery device shown in  FIGS. 1 and 2  can readily be used in active configurations such as spinning, vibration and forced airflow source. Spinning the drug delivery device about its long axis would serve the purpose of spreading the drug out against the first chamber walls, creating a large dose surface area to facilitate rapid metered fluidization. Similarly, vibration from an “Active” source would facilitate drug dispersion. The active vibration source could be a piezo-electric actuator or a motor. The active configuration alternatively could use an active air flow source such as compressed air or a fan. In this case, the entrained dose would likely be captured in a mixing chamber before being delivered to the patient. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. 
         [0058]      FIG. 3  illustrates a device similar to that shown in  FIG. 2  except that a second chamber has been added to store the drug dose. The second chamber provides benefits including secure containment of the drug dose, ease of manufacturing and drug filling, and drug metering. The second chamber can move relative to the first chamber and has an open and closed position. To open the package, plunger  305  pierces the moisture barrier and pushes against the second chamber causing it to slide from the closed position to the open position. Air flows through the plunger, around and through the second chamber and out the other side of the moisture bather. Drug is entrained into the air path by venturi effect through openings in the second chamber. The airflow through and around the second chamber is managed by air channels formed by the first chamber and the second chamber. The air channels are shaped to create a restriction at the second chamber openings, increasing the air velocity, and creating the venturi effect. 
         [0059]    Moisture barrier  301  is formed of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  301  when attached together. One layer has a formed step  308  that interfaces with outlet ring  303 . 
         [0060]    Internal opening mechanism  302  resides within moisture barrier  301  and creates first chamber  309 . First chamber  309  has openings for air inlet  312  and outlet  311 . Inlet  312  and outlet  311  are in close proximity with the moisture barrier  301  when the package is assembled. There is a first cutting edge  306  at outlet opening  311  in first chamber  309  and second cutting edge  307  integrated into a protuberance on plunger  305 . 
         [0061]    Second chamber  316  resides within first chamber  309  and contains the drug dose. Second chamber has a drug sealing system with openings  304  that are covered by interference with the internal opening mechanism  302  when the device is stored in its closed position. Second chamber  316  can be moved relative to first chamber  309  to eliminate the interference at the openings  304  to create a path between the first and second chambers. Integrated into second chamber  316  is a drug metering system in the form of one or more openings designed to fluidize powder in second chamber  316  and facilitate dose entrainment into the air path through first chamber  309  by venturi effect. Second chamber plug  317  is used to close an opening after filling second chamber  316  with drug during manufacturing. 
         [0062]    Air channels  318  direct airflow past second chamber openings  304  and through the device and are formed into the first chamber  309  and the walls of second chamber  316 . These air channels  318  could also take the form of a nozzle or orifice. 
         [0063]    To open the device and release the drug, plunger  305  and outlet ring  303  are moved together, causing the protuberance on plunger  305  to pierce moisture barrier  301  at inlet opening  312  to first chamber  309 . The protuberance on plunger  305  moves into first chamber  309  until plunger  305  contacts second chamber  316 , causing it to open by movement from the closed to open position. The protuberance on plunger  305  continues to move into first chamber  309  until plunger shoulder  313  contacts internal opening mechanism  302  at the inlet opening edge  314 . As plunger  305  continues to move towards outlet ring  303 , internal opening mechanism  302  slides against moisture barrier  301 , causing first cutting edge  306  to protrude through moisture barrier  301  at outlet opening  311 . Moisture barrier  301  deforms  310  to allow the relative movement of plunger  305  and outlet ring  303 . 
         [0064]    Air can be drawn through the open first chamber  309 , possibly through plunger  305 , and around and through second chamber  316  to entrain drug into the air stream. Dose metering system  304 , embodied by specific opening geometry in second chamber  316 , prevents the drug from leaving the package as one large clump and helps fluidize the dose. 
         [0065]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing second chamber  316  into multiple cavities, or by including multiple second chambers  316  within the device. 
         [0066]      FIG. 4  illustrates a device similar to that shown in  FIG. 3 , except that the inhaler relies on an “Active” source for the air movement through the inhaler instead of the patient&#39;s inhaling capability. To ensure proper mixing and aerosolization, it is envisioned that the entrained dose may be captured in a mixing chamber  419  before being delivered to the user. A mixing chamber may be required if the active air source is at a higher pressure or flow rate than would want to be delivered directly to the user. The active airflow source could be compressed air or a fan. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. The airflow may be through, or around, plunger  405 . The other parts shown in  FIG. 4  are similar to those shown in  FIG. 3 . 
         [0067]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. 
         [0068]      FIG. 5  illustrates a device similar that shown in  FIG. 3  except that second chamber  516  is designed to vibrate to assist in dose metering and evacuation. Second chamber  516  provides benefits including secure containment of the drug dose, ease of manufacturing and drug filling, and drug metering. Second chamber  516  can move relative to the first chamber  509 . To open the package, plunger  505  pierces moisture barrier  501  and pushes against second chamber  516 , causing it to slide from the closed position to the open position. Air flows through plunger  505 , around and through second chamber  516  and out the other side of first chamber  509 . Powder is entrained into the air path by vibration caused by the movement of air around second chamber  516 . The airflow through and around second chamber  516  is controlled by air channels formed by the internal opening mechanism  502  and second chamber  516 . Second chamber  516  may be held in position by a protruding tether that is in contact with internal opening mechanism  502 . 
         [0069]    Moisture barrier  501  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  501  when attached together. Furthermore, the top layer has a formed step  508  that interfaces with outlet ring  503 . Internal opening mechanism  502  resides in moisture barrier  501  and creates first chamber  509 . 
         [0070]    First chamber  509  has openings for air inlet  512  and outlet  511 , which are in close proximity to moisture barrier  501  when the device is assembled. There is a first cutting edge  506  at outlet opening  511  in first chamber  509  and a second cutting edge  507  integrated into a protuberance on plunger  505 . 
         [0071]    Second chamber  516  resides within first chamber  509  and contains the drug dose. Second chamber  516  contains a drug sealing system including openings  504  that are covered by interference fit with the first chamber  5099  when the device is in its closed position. Second chamber  516  can be moved relative to first chamber  509  to eliminate the interference at openings  504  to open the device and create a path between the first and second chambers. 
         [0072]    Also integrated into second chamber  516  is a drug metering system in the form of one or more openings designed to fluidize powder in second chamber  516  and facilitate drug entrainment by vibration and venturi effect into the air path through first chamber  509 . Second chamber  516  has a protruding section  519  extending toward air path inlet  512  that attaches to the internal opening mechanism  502 . Protruding portion or geometry  519  is the only point of contact with the internal opening mechanism  502  when second chamber  516  is in the open position. Protruding geometry  519  is shaped to allow second chamber  516  to vibrate in response to surrounding airflow turbulence. For example, protruding geometry  519  may be a flexible beam (like a tuning fork tine) or a flexible tether (such as a string or chain). Second chamber plug  517  is used to close an opening after filling second chamber  516  with drug during manufacturing. 
         [0073]    To open the device and release the drug, plunger  505  and outlet ring  503  are moved together; causing protuberance  507  on plunger  505  to pierce moisture barrier  501  at the inlet opening  512  to first chamber  509 . Protuberance  507  on plunger  505  moves into first chamber  509  until plunger  505  contacts second chamber  516 , causing it to open by movement from the closed to open position. Protuberance  507  on plunger  505  continues to move into first chamber  509  until plunger shoulder  513  contacts internal opening mechanism  502  at the inlet opening edge  514 . As plunger  505  continues to move towards outlet ring  503 , internal opening mechanism  502  slides against moisture barrier  501 , causing cutting edge  506  to protrude through moisture barrier  501  at outlet opening  511 . Moisture barrier  501  deforms  510  to allow the relative movement of plunger  505  and outlet ring  503 . 
         [0074]    Air can be drawn through the open first chamber  509 , possibly through plunger  505 , and goes around and through second chamber  516 , causing second chamber  516  to vibrate, and entraining drug into the air stream. Dose metering system  504 , formed by the specific opening geometry in second chamber  516 , prevents the powder from leaving the package as one large clump and helps fluidize the dose. 
         [0075]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing second chamber  516  into multiple cavities, or by including multiple second chambers  516  within the device. 
         [0076]      FIG. 6  is similar to the device described and illustrated in  FIG. 5  except that the inhaler relies on an “Active” source for vibration of the drug dose chamber instead of the patient&#39;s inhaling capability to activate the system. The active vibration source could be a piezo-electric actuator or a motor, possibly integrated with plunger  605 . The active vibration source can couple to second chamber  616  at the plunger interface, internal opening mechanism  602 , or a combination of the two. An alternate configuration would be to locate the vibration source inside moisture barrier  601 . The vibration source could be a piezoelectric material, a specific component geometry that can be excited at target frequencies and amplitudes, or a magnetically coupled resonance receiver. The internal vibration source could be an independent component or be fully or partially integrated into internal opening mechanism  602 , moisture barrier  601 , second chamber  616  or a combination thereof. Electro-mechanical coupling can be accomplished by means of plunger  605 , which makes contact with the internal vibration source after piercing moisture barrier  601 . An alternate coupling scheme would allow electro-mechanical contact once the internal vibration source moved outside moisture barrier  601  and contacted the device during package opening. Coupling can also be achieved by making a non-physical electrical or magnetic connection with the internal vibration source, such as through inductive coupling. 
         [0077]    The active vibration configuration alternatively could use an active air flow source such as compressed air or a fan. In this case, the entrained dose would likely be captured in a mixing chamber (not shown) before being delivered to the patient. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. The active airflow through the package could be delivered through the plunger. 
         [0078]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. 
         [0079]      FIG. 7  is similar to the device described in conjunction with  FIG. 2  except that a second chamber has been added to store the drug dose. The second chamber provides benefits including secure containment of the drug dose, ease of manufacturing and drug filling, and drug metering into the air stream. The second chamber can move relative to the first chamber and has an open and closed position. To open the package, the plunger pierces the moisture barrier and pushes against the second chamber, causing it to slide from the closed position to the open position. Air may flow through the plunger, or around it, and possibly through the second chamber and out the other side of the moisture barrier. Powder exits through openings in the second chamber by a combination of tumbling, shaking and spinning, and is entrained into the air path. Powder may also exit the second chamber by venturi effect and/or by air flowing through the second chamber. The airflow around the second chamber may be managed by air channels formed by the first chamber. The air channels could be shaped to create a vortex or spinning of the air within the first chamber to facilitate tumbling and spinning of the second chamber. 
         [0080]    Moisture barrier  701  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  701  when attached together. The top layer has a formed step  708  that interfaces with matching outlet ring geometry  703 . 
         [0081]    An internal opening mechanism  702  resides in moisture barrier  701  and creates first chamber  709 . First chamber  709  has openings for air inlet  712  and outlet  711 , which are in close proximity with moisture barrier  701  when the device is assembled. There is a first cutting edge  706  at the outlet opening  711  in first chamber  709  and a second cutting edge  707  integrated into a protuberance on the plunger  705 . 
         [0082]    Second chamber  716  resides within first chamber  709  and contains the drug dose. Second chamber  716  has a drug sealing system  704  with the openings in second chamber being covered by interference fit with first chamber  709  when the device is in its closed position. Second chamber  716  can be moved relative to first chamber  709  internal opening mechanism  702  to eliminate the interference at the openings and create a path between the first and second chambers. 
         [0083]    Integrated into the second chamber is a drug metering system in the form of one or more openings designed to fluidize powder in second chamber  716  and facilitate drug entrainment, primarily by tumbling and spinning, into the air path through first chamber  709 . These openings can be at any location in second chamber  716  as required to obtain the desired functionality. Chamber plug  717  is used to close an opening in second chamber  716  after filling with drug during manufacturing. 
         [0084]    To open the package, plunger  705  and outlet ring  703  are moved together, which causes the protuberance on the plunger to pierce moisture barrier  701  at the-inlet opening  712  to first chamber  709 . Protuberance  707  on plunger  705  moves into first chamber  709  until plunger  705  contacts second chamber  716  causing it to open by movement from the closed to open position. Protuberance  707  on plunger  705  continues to move into first chamber  709  until plunger shoulder  713  contacts the internal opening mechanism  702  at the inlet opening edge  714 . As plunger  705  continues to move towards outlet ring  703 , internal opening mechanism  702  slides against moisture barrier  701 , causing cutting edge  706  to protrude through moisture barrier at outlet opening  711 . Moisture barrier deforms  710  to allow the relative movement of outlet ring  703  and internal opening mechanism  702 . 
         [0085]    Air can be drawn through the open first chamber  709 , around and possibly through second chamber  716 , tumbling or spinning second chamber  716  and entraining drug into the air stream. Mesh screen  719  restrains second chamber  716  within first chamber  709 , and may also prevent the drug from leaving the package as one large clump. 
         [0086]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing second chamber  716  into multiple cavities, or by including multiple second chambers within the device. 
         [0087]    The tumbling chamber drug package configuration can also be utilized in an active inhaler system.  FIG. 8  shows this configuration and its use is identical to that of  FIG. 7 , with the difference being that rather than relying on the patient&#39;s respiration for the air flow to create the tumbling action of second chamber  816 , an active compressed air or impellor system could be used. This may be particularly helpful in cases where the patient&#39;s airflow rate capabilities are diminished due to medical conditions. Correspondingly, with an active airflow source, it is envisioned that the entrained dose could be captured in a mixing chamber  820  before being delivered to the user. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. The airflow through the device can be delivered through, or around, plunger  805 . 
         [0088]    This design could also be applied to a combination dose configuration where multiple drugs are delivered to the patient at the same time. 
         [0089]      FIG. 9  illustrates a device similar to the device of  FIG. 2 , except that a second chamber  916  has been added to store the drug dose. Second chamber  916  provides benefits including secure containment of the drug dose, ease of manufacturing and drug filling, and drug metering into the air stream. Second chamber  916  can move relative to internal opening mechanism  902 . To open the device, plunger  905  pierces moisture barrier  901  and pushes against second chamber  916 , causing it to slide from the closed position to the open position. Air may flow through plunger  905 , and around and possibly through second chamber  916  and out the other side of moisture barrier. Powder exits through openings in second chamber  916  from the spinning action, and is entrained into the air path. Powder may also exit second chamber  916  by venturi effect and/or by air flowing through second chamber  916 . The airflow around second chamber  916  may be directed or controlled by air channels formed by first chamber  909  internal opening mechanism  902 . The air channels could be shaped to create a vortex or spinning of the air in first chamber  909  to facilitate spinning of second chamber  916 . 
         [0090]    Moisture barrier  901  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil are pre-formed to create moisture barrier  901  when attached together. Furthermore, the top layer has a formed step  908  that interfaces with the geometry of matching outlet ring  903 . 
         [0091]    Internal opening mechanism  902  resides within moisture barrier  901  and creates first chamber  909 . First chamber  909  has openings for air inlet  912  and outlet  911 , which are in close proximity with moisture barrier  901  when the device is assembled. There is a first cutting edge  906  at outlet opening  911  in first chamber  909  and a second cutting edge  907  integrated into a protuberance on the plunger  905 . 
         [0092]    Second chamber  916  resides within first chamber  909  and contains the drug dose. Second chamber  916  has a drug sealing system  904 , with the openings in second chamber  916  being covered by an interference fit with internal opening mechanism  902  when the device is in its closed position. Second chamber  916  can be moved relative to internal opening mechanism  902  to eliminate the interference at the openings and create a path between the first and second chambers. 
         [0093]    Integrated into second chamber is a drug metering system in the form of one or more openings designed to fluidize powder in second chamber  916  and facilitate drug entrainment, primarily by spinning, into the air path through first chamber  909 . The openings can be in any location on second chamber  916 . Chamber plug  917  is used to close an opening in second chamber  916  after filling with drug during manufacturing. 
         [0094]    To open the device, plunger  905  is moved toward the outlet ring  903  which causes the cutting edge on the plunger protuberance to pierce moisture barrier  901  at inlet opening  912  to first chamber  909 . The protuberance on plunger  905  moves into the first chamber  909  until plunger  905  contacts the second chamber  916  causing it to move from the closed to open position. The protuberance on plunger  905  continues to move into the first chamber  909  until plunger shoulder  913  contacts internal opening mechanism  902  at inlet opening edge  914 . As plunger  905  continues to move towards outlet ring  903 , internal opening mechanism  902  slides against moisture barrier  901 , causing cutting edge  906  to protrude through moisture barrier  901  at the outlet opening  911 . Moisture barrier deforms  910  to allow the relative movement of outlet ring  903  and internal opening mechanism  902 . 
         [0095]    Air can be drawn through the open first chamber  909 , around and possibly through second chamber  916 , spinning second chamber  916  and entraining drug into the air stream. Air inlets  918  can be configured to create a vortex within first chamber  909 , which imparts a spinning action on second chamber  916 . Second chamber  916  may have fins or other geometric details that are acted upon by the air to impart the spinning motion. Second chamber  916  is radially supported by first chamber  909  and a mesh screen  919  in order to guide the spinning motion. Mesh screen  919  also constrains second chamber  916  axially within first chamber  909 , and may also prevent the drug from leaving the package as one large clump. 
         [0096]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing the second chamber  916  into multiple cavities, or by including multiple second chambers within the device. 
         [0097]    The spinning chamber drug package configuration can also be utilized in an active inhaler system.  FIG. 10  shows this configuration and its use is identical to that of  FIG. 9 , with the difference being that rather than relying on the patient&#39;s respiration for the air flow to create the spinning action of second chamber  1016 , an active compressed air or impellor system could be used. This may be particularly helpful in cases where the patient&#39;s air flow rate capabilities are diminished due to medical conditions. Correspondingly, with an active airflow source, it is envisioned that the entrained dose could be captured in a mixing chamber  1020  before being delivered to the user. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. The airflow through the package can be delivered through, or around, plunger  1005 . 
         [0098]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. 
         [0099]      FIG. 11  illustrates a drug delivery device with a movable internal opening mechanism  1102  that contains the drug dose. Internal opening mechanism  1102  is located inside the drug sealing system  1103 . Drug sealing system  1103  is located within moisture barrier  1101  and is attached at seal  1114 , at least in part, to moisture barrier. Internal opening mechanism  1102  can move relative to moisture barrier  1101  and drug sealing system  1103 . Moisture barrier  1101  is opened when cutting edge  1105  on internal opening mechanism  1102  is pressed against moisture barrier  1101 . The drug dose exits through an opening  1106  by centrifugal force as the package is rotated (spinning action) about a main axis of rotation  1107 . In alternate configurations, powder may also exit the internal opening mechanism by a venturi effect and/or by air flowing through internal opening mechanism  1102 . 
         [0100]    This configuration provides benefits including secure containment of the drug dose, ease of manufacturing and drug filling, and drug metering into the air stream. 
         [0101]    Moisture barrier  1101  is comprised of two layers of a moisture impervious material, typically a plastic coated foil. The top and bottom layers of foil may be pre-formed to create the moisture barrier  1101  when attached together. Drug sealing system  1103  resides within moisture barrier  1101  and may create a first chamber  1115 . The internal opening mechanism  1102  resides within first chamber  1115 , and forms second chamber  1109 . The drug dose resides inside second chamber  1109 . 
         [0102]    Second chamber  1109  has a plugged opening  1104  on one side for drug filling during manufacturing. The internal opening mechanism has a first cutting edge  1105  in close proximity to the foil of moisture barrier  1101 . There is also a seal  1114  between drug sealing system  1103  and moisture barrier  1101  formed by means of a heat seal or interference fit. Internal opening mechanism  1102  creates a friction fit seal  1116  with drug sealing system  1103  to keep the drug from migrating out of second chamber  1109  prior to use. Drug sealing system  1103  may also extend around internal opening mechanism  1102  to guide its motion during opening of moisture barrier  1101 . 
         [0103]    To open the device package, internal opening mechanism  1102  is moved relative to moisture barrier  1101  so that first cutting edge  1105  pierces moisture barrier  1101 . The motion of internal opening mechanism  1102  is caused by spinning the packaging device, creating centrifugal force which moves internal opening mechanism  1102  away from the axis of revolution  1107 . In a passive system, the patient&#39;s inspiratory airflow would be used to spin the packaging device. In an active system, the spinning can be accomplished by means of an active spinning source  1108 , such as a motor. An active configuration allows for stable control of rotational speed, and can provide higher opening speeds which allows thicker, formable foils to be used. 
         [0104]    The speed at which piercing occurs can be controlled by a variety of factors, including the mass of internal opening mechanism  1102  and contained drug, the distance of the center of this mass from the axis of revolution  1107 , the thickness of the moisture barrier  1101  foil layer, and the geometry of first cutting edge  1105 . The ability to dictate the piercing speed has a number of potential benefits. In a passive system, where the rotation of the packaging device is caused by the patient&#39;s inspiratory air flow, the rotational speed at packaging device opening can be used to ensure that a minimum inspiratory flow rate is met prior to packaging device opening. In addition, in both passive and active systems, specific package opening speeds may allow for control of powder dispersion out of second chamber  1109  at predetermined rates. 
         [0105]    Following piercing of moisture barrier  1101  by the internal opening mechanism  1102 , the drug dose exits second chamber  1109  and is entrained in the air flow by means of centrifugal force. The rate of drug metering out of the packaging device can be controlled by means of the geometry of opening  1106  in internal opening mechanism  1102  as well as by the speed of rotation. It is envisioned that the drug dose may enter a mixing chamber  1112  before being delivered to the user. The drug exits mixing chamber  1112  through outlet mouthpiece  1113 . 
         [0106]    Piercing of moisture barrier  1101  by internal opening mechanism  1102  can also be achieved by means of an actuating mechanism  1110  rather than relying on centrifugal force caused by spinning of the device. This may be particularly useful in a passive system where it may be difficult to achieve high rotational speeds using the patient&#39;s inspiratory airflow alone. 
         [0107]    This design could also be applied to a combination dose configuration where multiple drugs are delivered to the patient at the same time. 
         [0108]      FIG. 12  illustrates a multi-dose drug delivery device that integrates the systems illustrated in  FIGS. 1-11  and  13 - 14  and has the benefit of packaging multiple doses into a single dispensing system to simplify the user experience. 
         [0109]    The dose packaging is manufactured in strips made up of multiple, factory pre-metered unit-doses  1204  that are positioned in a circular array and mounted between a two-piece clamshell cassette  1203 . The dose packaging can be color coded to help identify drug type and dose strength. 
         [0110]    The air path through each unit-dose is directed in an outward radial direction. A plunger  1205  is located at the center of cassette  1203  and has an outward motion during unit-dose packaging device opening. A mouthpiece  1206  is located on the outside of cassette  1203  and is aligned with the central axis of the first unit-dose  1212 . A mouthpiece cover  1202  is attached to a mechanism  1213  designed to actuate plunger  1205 , advance drug cassette  1203  and advance dose counter  1207 . 
         [0111]    Generally, to operate the multi-dose inhaler the user rotates mouthpiece cover  1202  from the closed position  1208  to a first position  1209 , exposing mouthpiece  1206 . The user then rotates mouthpiece cover  1202  to a second position  1210 . This motion  1211  drives plunger  1205  in a radial direction, opening the unit-dose package  1204  that is aligned with plunger axis  1212 . Plunger  1205  may be connected to mouthpiece cover  1202  by a mechanical linkage, or, alternatively, there may be a separate mechanism that causes the motion of the plunger that is not tied to the mouthpiece cover. 
         [0112]    The user inhales to administer the drug dose, and then moves mouthpiece cover  1202  back to closed position  1208 . The action of closing the mouthpiece cover advances unit-dose cassette  1203  to the second unit-dose position and advances dose counter  1207  by one number. 
         [0113]    The multi-dose inhaler design also integrates a dose readiness indicator. The internal opening mechanism inside each dose package can be color coded for visibility. As each dose package is opened the internal opening mechanism is exposed and can be made visible to the user by means of a window in the cassette. Exposed color (green) can indicate that the dose is ready for inhalation. 
         [0114]    Dose cassettes  1203  can be designed to be replaceable. In addition, the user can load cassettes with specific drug dose therapies by opening the cassette and replacing spent doses in a reusable configuration. 
         [0115]      FIGS. 13A and 13B  show a variant of the drug delivery system of the invention using a shaped dose metering system to assist in dispersing the medicine into the air path.  FIG. 13A  shows the device in the closed position while  FIG. 13B  shows it in the open position. The drug delivery system includes a first chamber, an opening device, and a dose metering system. 
         [0116]    First chamber  1301  is comprised of two layers of material, typically a plastic. The top and bottom layers are pre-formed to create an air path  1302  when attached together. A dose metering system  1303  is formed into the walls of first chamber  1301  to assist in drug dispersion. The drug resides in a reservoir  1304  in proximity to dose metering system  1303  when the device is closed and the drug is dispersed into the air path after opening the device. Dose metering system  1303  is in the form of a geometry designed to divert, deflect or direct some portion of airflow from the first chamber into reservoir  1304 . Reservoir  1304  is shaped to receive airflow diverted from the air path  1302  through first chamber  1301 , causing the medicine to fluidize and move about reservoir  1304 . 
         [0117]    First chamber  1301  has air inlet  1305  and air outlet  1306 , which are closed by barriers  1307  when the device is assembled. The airflow is managed by air channels formed by the first chamber and the geometry enclosing the air path. 
         [0118]    An opening mechanism (not shown) punctures barriers  1307  to open the air pathway  1302 . Air can be drawn through open air pathway  1302 , and possibly through the opening mechanism, thereby entraining drug into the air stream. Dose metering system  1303  facilitates fluidization and dispersion of the drug. 
         [0119]    Dose metering system  1303  includes a shaped opening  1308 . Shaped opening  1308  has a geometry designed to control the movement of airflow in, out and around reservoir  1304  as air moves along air path  1302 . 
         [0120]    The drug delivery device shown in  FIGS. 13A and 13B  can readily be used in active configurations such as vibration and forced airflow source. Vibration from an “Active” source would facilitate drug dispersion. The active vibration source could be a piezo-electric actuator or a motor. The active configuration alternatively could use an active air flow source such as compressed air or a fan. In this case, the entrained dose would likely be captured in a mixing chamber before being delivered to the patient. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. 
         [0121]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing reservoir  1304  into multiple cavities, or by including multiple reservoirs  1304  within the device. 
         [0122]      FIGS. 14A and 14B  illustrate a drug delivery device that is similar to that of  FIG. 13  except that the geometry of opening mechanism  1402  defines a portion of first chamber  1403  and air path  1401 . Opening mechanism  1402  is movable from a closed position to an open position and is movable relative to reservoir  1404 . This configuration provides benefits including secure containment of the drug.  FIG. 14A  shows the device in the closed position and  FIG. 14B  shows it in the open position. 
         [0123]    First chamber  1403  is comprised of two parts and typically is made of plastic. In the illustrated embodiment, opening mechanism  1402  and first chamber  1403  are pre-formed to create a closed air path  1401 . Air path  1401  has openings for air inlet  1407  and outlet  1408 . 
         [0124]    Reservoir  1404  contains the drug dose. Opening mechanism  1402  includes a drug sealing system  1405  that covers the opening to reservoir  1404  by interference fit when the device is stored in the closed position. Opening mechanism  1402  can be moved relative to reservoir  1404  to eliminate the interference at the opening to create an air path between first chamber  1403  and reservoir  1404 . Integrated into first chamber  1403  is a drug metering system  1406  in the form of one or more shaped openings designed to fluidize powder in reservoir  1404  and facilitate drug entrainment into air path  1401 . 
         [0125]    Air path  1401  directs airflow past drug metering system  1406  and through the device. The air path can be shaped to create a restriction at the drug metering system, increasing velocity, and thereby increasing the effect of drug metering system  1406 . Drug metering system  1406  is shaped to divert airflow into, and/or out of reservoir  1404 , fluidizing the drug. Drug is entrained from the reservoir into the airflow by a combination of venturi effect, centrifugal force and turbulence created at the opening to the reservoir. 
         [0126]    To open the device, opening mechanism  1402  is moved from the closed position to the open position. This action opens air path  1401  through first chamber  1403 . This action also moves integral dose sealing system  1405  which opens up an air path between first chamber  1403  and reservoir  1404 . 
         [0127]    Air can be drawn through inlet opening  1407 , through air path  1401 , across drug metering system  1406  and out outlet opening  1408 , entraining drug into the air stream. Dose metering system  1406 , embodied by specific opening geometry in the reservoir, prevents the powder from leaving the package as one large clump and helps fluidize the dose. 
         [0128]    This design could also be applied in a combination dose configuration where multiple drugs are delivered to the patient at the same time. Typically, the drugs need to be stored separately from each other and then combined at the time of inhalation. This can be accomplished by dividing reservoir  1404  into multiple cavities, or by including multiple reservoirs  1404  within the device. 
         [0129]    The drug delivery device shown in  FIGS. 14A and 14B  can readily be used in active configurations such as vibration and forced airflow source. Vibration from an “Active” source would facilitate drug dispersion. The active vibration source could be a piezo-electric actuator or a motor. The active configuration alternatively could use an active air flow source such as compressed air or a fan. In this case, the entrained dose would likely be captured in a mixing chamber before being delivered to the patient. The mixing chamber could be a rigid vessel or a flexible design that inflates during use and collapses for storage. 
         [0130]    The system of the present invention provides significant advantages not seen in the prior art. The system provides a sealed, protected environment for a substance and prevents exposure of the substance from degrading elements for an extended period of time. For example, the system can provide a moisture-impervious environment for moisture-sensitive substances, such as medicines in powdered form. The use of an integrated, internal puncturing mechanism (if applicable) facilitates release of the substance from the packaging device without relying on external components. The puncturing mechanism may be easily actuated, for example, by sliding the puncturing mechanism (i.e., the tube) within the internal chamber of the packaging device or a plunger may be used. The components of the packaging device are designed for manufacturability and the packaging device may be assembled and filled quickly and efficiently. The integrated puncturing mechanism provides a clear, unobstructed path for the substance stored in the packaging device to exit and reduces the number of dead spots or edges that trap the substance, a feature common in capsules that utilize external puncturing mechanisms. Moreover, the ability to create an air path through an internal chamber of a packaging device allows direct delivery of the substance, without requiring transfer of the substance to a separate delivery chamber. The integrated puncturing mechanism facilitates complete evacuation of all of the substance from the packaging device interior, resulting in more accurate dosing, increased safety and reduced waste. 
         [0131]    The present invention has been described relative to illustrative embodiments. Since certain changes may be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings be interpreted as illustrative and not in a limiting sense. 
         [0132]    It is also to be understood that the following claims are to cover all generic and specific features of the invention described herein, and all statements of the scope of the invention which, as a matter of language, might be said to fall there between.