Patent Publication Number: US-2021178088-A1

Title: Liquid nebulization systems and methods

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. Nonprovisional Application No. 14/743,711, filed on Jun. 18, 2015, entitled “LIQUID NEBULIZATION SYSTEMS AND METHODS,” which claims the benefit of U.S. Provisional Application No. 62/019,781, filed on Jul. 1, 2014, entitled “LIQUID NEBULIZATION SYSTEMS AND METHODS,” the entire disclosures of which are hereby incorporated by reference, for all purposes, as if fully set forth herein. 
    
    
     BACKGROUND OF THE INVENTION 
     Aerosolization systems provide effective delivery for a variety of medicaments, such as insulin and asthma medications. Such systems deliver the medicaments directly to a user&#39;s respiratory system by aerosolizing a metered dose of the medicament in liquid form. The user then inhales the aerosolized medicament directly into the respiratory system, enabling faster treatment of various medical conditions. 
     Delivery of consistent and properly metered doses of aerosolized medicament to a user is very important. Current aerosolization systems often provide inconsistent doses by having some of the medicament remain in a reservoir in liquid form after the aerosolization process. Additionally, the aerosolized medicament is often delivered with too great or too little force for substantially all of the metered dose to properly enter the user&#39;s respiratory system. A further problem of current aerosolization systems is a tendency for the medicament to become contaminated by the user or other sources. Contamination of the medicament is particularly problematic since some or all of the contaminated medicament is thereafter delivered directly to the user&#39;s respiratory system. Embodiments of the invention may provide solutions to these and other problems. 
     BRIEF SUMMARY OF THE INVENTION 
     In one embodiment, an aerosolization device for delivering aerosolized medicament to a user is provided. The aerosolization device may include a conduit, an aerosol generator in communication with the conduit, a fluid receiving chamber in communication with the aerosol generator, a restrictor disposed within the conduit, and an indicator mechanism. The conduit may have an inner wall and a mouthpiece end by which a user may cause an inspiratory flow through the conduit. The aerosol generator may include a vibratable mesh where the vibratable mesh may be laterally offset from the inner wall. The fluid receiving chamber may receive a volume of a liquid medicament. At least a portion of the fluid receiving chamber may be tapered such that substantially all of the liquid medicament may be directed onto the vibratable mesh for aerosolization. The restrictor may define a plurality of apertures. The plurality of apertures may be configured to provide an increase in pressure differential that varies with an inspiratory flow rate within the conduit and to provide a relatively laminar flow downstream of the restrictor compared to upstream of the restrictor plate. The indicator mechanism may indicate to a user a state of one or more flow parameters relative to a predefined desired range. The aerosol generator may be configured to aerosolize at least a portion of the volume of the liquid medicament only when the one or more flow parameters of the inspiratory flow are within the desired range. 
     In another embodiment, a different aerosolization device for delivering aerosolized medicament to a user is provided. The aerosolization device may include a conduit, an aerosol generator in communication with the conduit, and a fluid receiving chamber in communication with the aerosol generator. The conduit may be attachable to a housing. The conduit may have an inner wall and a mouthpiece end by which a user may cause an inspiratory flow through the conduit. The aerosol generator may include a vibratable mesh. The vibratable mesh may be laterally offset from the inner wall by about 1 millimeter (mm) and 6 mm. The aerosol generator may receive a volume of a liquid medicament and at least a portion of the fluid receiving chamber may be tapered such that substantially all of the liquid medicament may be directed onto the vibratable mesh for aerosolization. The aerosol generator may be configured to aerosolize at least a portion of the volume of liquid medicament only when one or more flow parameters of an inspiratory flow are within a predefined desired range. 
     In another embodiment, a method of delivering an aerosolized medicament to a user&#39;s respiratory system is provided. The method may include sensing a state of a flow parameter of an inspiratory flow within a conduit. The conduit may have an inner wall and a mouthpiece end by which a user may cause the inspiratory flow within the conduit. The method may also include vibrating a mesh of an aerosol generator in communication with the conduit to aerosolize a volume of a liquid medicament to produce a plume of aerosolized medicament within the conduit when the state of the flow parameter is within a predefined desired range. The mesh may be laterally offset from the inner wall. The plume of aerosolized medicament may be carried toward the mouthpiece end of the conduit. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention is described in conjunction with the appended figures: 
         FIG. 1A  depicts an interior of an aerosolization device according to embodiments of the invention; 
         FIG. 1B  shows a cross section of  FIG. 1A  according to embodiments of the invention; 
         FIG. 2  depicts a front of the aerosolization device of  FIG. 1A  according to embodiments of the invention; 
         FIG. 3  illustrates a housing of the aerosolization device of  FIG. 1A  with the conduit and aerosol generator removed according to embodiments of the invention; 
         FIGS. 4A and 4B  depict the conduit and aerosol generator of the aerosolization device of  FIG. 1  removed from the housing according to embodiments of the invention; 
         FIG. 5  illustrates restrictor plates according to embodiments of the invention; 
         FIG. 6  shows a restrictor plate within a conduit of an aerosolization device according to embodiments of the invention; 
         FIG. 7  shows laminar flow created by a restrictor plate within the conduit of  FIG. 6  according to embodiments of the invention 
         FIGS. 8A-8C  depict conduits having mouthpiece ends at various angles according to embodiments of the invention; 
         FIG. 9  shows an input device on an aerosolization device according to embodiments of the invention; and 
         FIG. 10  is a block diagram of a method of using an aerosolization device according to embodiments of the invention. 
     
    
    
     In the appended figures, similar components and/or features may have the same numerical reference label. Further, various components of the same type may be distinguished by following the reference label by a letter that distinguishes among the similar components and/or features. If only the first numerical reference label is used in the specification, the description is applicable to any one of the similar components and/or features having the same first numerical reference label irrespective of the letter suffix. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The ensuing description provides exemplary embodiments only, and is not intended to limit the scope, applicability or configuration of the invention. Rather, the ensuing description of exemplary embodiments will provide those skilled in the art with an enabling description for implementing various embodiments of the invention. It will be understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope of the invention as set forth in the appended claims. For example, any detail discussed with regard to one embodiment may or may not be present in variations of that embodiment, and/or in other embodiments discussed herein. 
     Embodiments of an aerosolization device for assisting in proper delivery of an uncontaminated dose of aerosolized medication to a user&#39;s respiratory system are described herein. In many embodiments, liquid medicament may be provided to an aerosolization device in a metered dose. The liquid medicament may be dispensed to an aerosol generator. In some embodiments, the liquid medicament may be provided via a chamber or reservoir that funnels the liquid medicament into the aerosol generator where the liquid medicament is aerosolized for delivery into a user&#39;s respiratory system. In some embodiments, a separate container holding the liquid medicament may couple with the aerosolization device to provide the liquid medicament thereto. The aerosol generator may be configured to aerosolize at least a portion of the volume of the liquid medicament only when the one or more flow parameters of the inspiratory flow are within a desired range. 
     In some embodiments, the aerosolization device may include a conduit, an aerosol generator in communication with the conduit, a fluid receiving chamber in communication with the aerosol generator, a restrictor plate disposed within the conduit, and an indicator mechanism. In many embodiments, some or all of these components are disposed within a housing. In some embodiments, the conduit and/or the aerosol generator may be removably coupled with or received within the housing. By providing a removable conduit and/or aerosol generator, the aerosolization device may be easily cleaned, thus preventing contamination and buildup of pathogens and/or other contaminants. The removal of the components also helps in drying the components. As the aerosolization device is quickly and easily cleaned and dried in this manner, no standing liquid remains that could lead waterborne bacteria to proliferate. 
     In some embodiments, the conduit may include an inner wall and a mouthpiece end by which a user may cause an inspiratory flow through the conduit. A user may inhale through the mouthpiece to create the inspiratory flow of air that may transport an aerosolized medicament to the user. In some embodiments, the mouthpiece end of the conduit may deliver the aerosolized medicament to the user at an angle relative to a horizontal plane. Such a delivery angle may be selected based on the dosage and type of medicament to be delivered to the user&#39;s respiratory to ensure that a substantial portion of the aerosolized medicament is delivered to the respiratory system without becoming stuck in the user&#39;s mouth, throat, and/or other area. 
     In many embodiments, a sensor is used to determine when a parameter of the inspiratory flow is within a predefined desired or operating range of the aerosolization device and/or the aerosol generator. For example, a flow sensor or pressure transducer may be used to determine a flow rate or pressure differential within the conduit. Other types of sensors and flow parameters may also be employed/measured. For example, the flow parameter can be an inspiratory flow rate, inspiratory pressure, inspiration time, and the like detected by a flow sensor, timer, pressure transducer, or other sensing mechanism. A processing unit coupled with the sensor may compare the sensed value to a stored desired range. In some embodiments, the desired range of a flow parameter for a particular medicament delivery may correspond to the operating range of the aerosol generator. In other embodiments, the desired range of a flow parameter may be narrower or broader than the operating range of the aerosol generator. 
     In some embodiments, the aerosol generator may include a vibratable mesh that is in fluid communication with the conduit. The vibratable mesh may be domed shaped and be vibrated by an annular piezoelectric element (not shown) or other electro-mechanical resonating device that circumscribes the vibratable mesh. The vibratable mesh is vibrated when one or more flow parameters are within an operating range of the aerosol generator. For example, a flow sensor and/or pressure transducer in communication with the conduit may detect that an inspiratory flow rate and/or a pressure differential within the conduit is within an operating range of the aerosol generator. A processor may control a circuit to provide an electric current to the piezoelectric element to vibrate the mesh. Typically, the vibratable mesh will be vibrated at a frequency in the range from about 50 kHz to about 150 kHz to aerosolize the dose of liquid medicament. 
     The vibratable mesh may be disposed at a distance from the inner wall of the conduit such that a lower surface of the vibratable mesh is offset from the most proximate wall of the conduit. This offset ensures that substantially all of any pathogens or other contaminants that are introduced to the conduit will be deposited onto surfaces other than the vibratable mesh, thereby maintaining a clean and/or sterile source of aerosolized medicament. Such pathogens and/or contaminants may be introduced to the aerosolization system by the user via a cough, sneeze, or other action or by an environmental source. 
     In some embodiments, the vibratable mesh may define a plurality of apertures. The plurality of apertures may include more than 500 apertures. In some embodiments, the plurality of apertures may include more than 1000 apertures. Each aperture may have an exit diameter ranging from about 1 μm to about 8 μm, preferably from about 3 μm to about 6 μm, and in some cases around 4 μm. Due to the combination of small aperture size and being offset from the conduit, the vibratable mesh and reservoir can stay substantially clean to produce an uncontaminated plume of aerosolized medicament. 
     In some embodiments, the fluid receiving chamber may receive a volume of a liquid medicament to be aerosolized. Any medicament that is not deposited directly onto the vibratable mesh can be funneled or otherwise directed onto the vibratable mesh by tapered walls of the fluid receiving chamber such that substantially all of the liquid medicament may be directed onto the vibratable mesh for aerosolization. The fluid receiving chamber can be configured to have not more than 15 μl of the liquid medicament remain within the fluid receiving chamber after aerosolization. By dispensing the entire dose or substantially all of the dose, the vibratable mesh is kept essentially free of liquid from one dose to the next. Any remaining liquid will air dry between doses. In some instances, the time between doses may be between about 45 minutes and 2 hours. In this way, it is thereby possible to avoid contact between liquid and ambient air during periods of non-use between successive uses. For pharmaceutical preparations this is particularly important since it may obviate the need for the use of preservatives in the liquid and avoids evaporative losses. For example, various preservative free insulin formulations that may be used include those described in U.S. application Ser. No. 13/004,662, entitled “Preservative Free Insulin Formulations and Systems and Methods for Aerosolizing,” which is hereby incorporated by reference in its entirety. 
     In many embodiments, the inhaled air may pass through a restrictor array within the conduit. In some embodiments, the restrictor array may be a restrictor plate that has a plurality of apertures passing therethrough. As air passes through the apertures, the apertures provide an increase in pressure differential that varies according to the inspiratory flow rate within the conduit. The apertures also provide a relatively laminar flow downstream of the restrictor plate compared to upstream of the restrictor plate. In many embodiments, the apertures are disposed along an outer periphery of the restrictor plate. In some embodiments, the vibratable mesh may be located downstream of the restrictor plate or other restrictor array and produce a plume of aerosolized medicament within the relatively laminar flow produced by the restrictor array. In some embodiments, the restrictor array may include multiple restrictor plates in series. 
     The indicator mechanism may indicate to a user a state of a parameter of the inspiratory flow relative to a predefined desired range. For example, the indicator may be a light, analog/digital display or readout, speaker, vibration-generating device, and/or other feature that alerts a user as to the state of the parameter. In some embodiments, the state of the parameter can be an inspiratory flow rate, inspiratory pressure, inspiration time, and the like detected by a flow sensor, timer, pressure transducer, or other sensing mechanism. The indicator may inform the user if they are within or outside of the desired range for the parameter. 
     In some embodiments, an ‘end of dose’ indication can be provided to a user when an entire dose of the medicament has been aerosolized. Such an indication may be provided upon a sensor, such as a load or flow sensor, detects that substantially all of the medicament has been aerosolized. Another indication may also be provided to the user informing them of when the liquid medicament is actually being aerosolized by the activated vibratable mesh. Such indications can be provided by the indicator mechanism described above, such as by providing a distinguishable indication from the indication of the state of the flow parameter. For example, the state of the flow parameter may be indicated by a green light and the indication of the end of dose may be provided by a blue light. In other embodiments, the end of dose indication and/or the aerosolization indication may be provided by one or more separate indicator mechanisms. 
     In some embodiments, the aerosolization device may further include an input device for receiving and setting the predefined desired range of the parameter of the inspiratory flow. For example, the input device may include a barcode scanner, radio frequency identification (RFID) reader, keyboard, or any other input device that can receive an input from the user regarding one or more parameters of the inspiratory flow, such as a desired flow rate, inspiratory pressure, or inspiration time. In some embodiments, the desired flow rate may be visually or otherwise encoded on the medicament delivery container, and read by the aerosolization device therefrom. 
     In some embodiments, the parameter of the inspiratory flow may include the inspiratory flow rate within the conduit. The predefined desired range of the inspiratory flow rate may be between about 5 and 14 liters per minute (L/min). In some embodiments, the parameter of the inspiratory flow may include the inspiration time. The predefined desired range of the inspiration time may be between about 5 and 26 seconds. In some embodiments, multiple parameters may be measured and referred to. For example, in one embodiment, a certain amount of inspiration time of a minimum inspiratory flow may be necessary. 
     In some embodiments, the aerosolization system may include electronic elements including, but not limited to, a processing element and a memory unit. The processing element may be used to control the actuation of the aerosol generator, indicator mechanisms, and input devices, as well as any sensors such as flow sensors and pressure transducers. The memory unit may be configured to store settings and ranges set by the input device for the parameters of the indicator mechanism and/or aerosol generator. The memory unit may also be configured to store data related to past aerosolization sessions, as well as information provided by medicament delivery vessels attached thereto. 
     Turning now to the drawings,  FIGS. 1A and 1B  illustrate an aerosolization device  100 , in accordance with various embodiments of the invention. Aerosolization device  100  includes a conduit  102  and an aerosol generator  104  in communication with the conduit  102 . The aerosolization device  100  may also include one or more indicator mechanisms  106 , shown here as indicator lights. The one or more indicator mechanisms may be coupled with a housing  108  or some other portion of device  100 . Conduit  102  and aerosol generator  104  may also optionally be coupled with housing  108 . 
     In some embodiments, conduit  102  may include a mouthpiece end  110  through which a user may inhale to produce an inspiratory flow to deliver aerosolized medicament to the user&#39;s respiratory system. As seen in  FIG. 1B , the conduit  102  defines an inner wall  120 . The aerosol generator  104  may include a vibratable mesh  112 . Liquid medicament can be dispensed onto the vibratable mesh  112 , either directly from a vial of liquid medicament or indirectly by being funneled onto the vibratable mesh  112  by tapered walls of a fluid receiving chamber  114 . In many embodiments, the vibratable mesh  112  is vibrated via a mechanism controlled by a processor to aerosolize a volume of liquid medicament when a flow rate of the inspiratory flow is within an operating range of the aerosol generator  104 . When vibrated, the vibratable mesh  112  operates to produce a plume of aerosolized medicament within the conduit  102  such that the aerosolized conduit can be inhaled into the user&#39;s lungs. 
     Exemplary aerosol generators that can be used are also described in U.S. Pat. Nos. 5,164,740; 6,629,646; 6,926,208; 7,108,197; 5,938,117; 6,540,153; 6,540,154; 7,040,549; 6,921,020; 7,083,112; 7,628,339; 5,586,550; 5,758,637; 6,085,740; 6,467,476; 6,640,804; 7,174,888; 6,014,970; 6,205,999; 6,755,189; 6,427,682; 6,814,071; 7,066,398; 6,978,941; 7,100,600; 7,032,590; 7,195,011, incorporated herein by reference. These references describe exemplary aerosol generators, ways to manufacture such aerosol generators and ways to supply liquid to aerosol generators, and are incorporated by reference for at least these features. 
     In some embodiments, the vibratable mesh may be disposed at a distance  122  from the inner wall  120  of the conduit  102 . For example, vibratable mesh  112  may be disposed at a distance  122  between about 1 mm and 6 mm from the inner wall  120 . The vibratable mesh  112  may define a plurality of apertures from which the aerosolized medicament is dispersed into the conduit  102 . In some embodiments, the plurality of apertures may include more than  500  apertures, each aperture having a diameter between about 1 and 8 μm. In other embodiments, the plurality of apertures may include more than 1000 apertures. The small size of the apertures in conjunction with the vibratable mesh  112  being offset from the conduit  102  helps ensure that the aerosolized medicament is uncontaminated. The vibratable mesh  112  may be dome shaped and be vibrated by an annular piezoelectric element (not shown) that circumscribes the apertures. The diameter of the vibratable mesh  112  may be in the range from about 5 mm to about 8 mm. The vibratable mesh  112  may also have a thickness in the range from about 50 microns to about 70 microns. Typically, the vibratable mesh  112  will be vibrated at a frequency in the range from about 50 kHz to about 150 kHz to aerosolize the dose of liquid medicament. 
     In some embodiments, the conduit  102  may include an opening  134  that provides access to the fluid receiving chamber  114 . The opening  134  may have a diameter that is smaller than a diameter  136  of a top of the fluid receiving chamber  114 . Such geometry ensures that sides of a tip of a dispenser of liquid medicament cannot contact the walls of the fluid receiving chamber  114 , and also provides a contact point for a shoulder of a dispensing mechanism to prevent the dispenser tip from contacting the vibratable mesh  112 . By preventing such contact, the tip cannot contact a volume of liquid medicament within the fluid receiving chamber  114  and pull some of the volume out of the fluid receiving chamber  114  and/or contaminate the liquid medicament. 
     In some embodiments, the aerosolization device  100  include a processing unit or integrated circuit (IC)  138  that controls the function of or runs computer code to control other electronic components of the aerosolization device  100 . Aerosolization device  100 , including IC  138 , may be powered by batteries  140  that are coupled with IC  138 . IC  138  may be electrically coupled with electronic components, such as any sensors, indicating mechanisms  106  and/or a piezoelectric element of aerosol generator  104 . IC  138  can control the actuation of the indicator mechanisms and/or the aerosol generator  104  based on information received from any sensors, such as flow sensors or pressure transducers in fluid communication with the conduit  102 . In some embodiments, IC  138  may be electrically coupled with the conduit  102  and/or the aerosol generator  104  using a plug  124 . The conduit  102  and/or aerosol generator  104  may be removable from housing  108 . The conduit  102  and/or aerosol generator  104  may be inserted into housing  108  and interfaced with plug  124  to supply power to and control actuation of the aerosol generator  104  based on measurements from sensors in fluid communication with conduit  102 . 
       FIG. 2  shows a top view of aerosolization device  100  and indicator mechanisms  106  according to embodiments of the invention. In some embodiments, indicator mechanisms  106  can include a breathing indicator  116  and a battery indicator  118 . Breathing indicator  116  can direct a user when and how to breath to maximize delivery of the aerosolized medicament to the user&#39;s lungs. In some embodiments, breathing indicator  116  can include multiple indicators, such as various colored LEDs, to provide the user more detailed guidance. Breathing indicator  116  may be in the shape of a chevron that includes 3 colors of LEDs. 
     In some embodiments, optimal pulmonary delivery of medicaments such as liquid insulin occurs at specified flow rates and inspiratory times. For example, an optimal flow rate may be between about 5 and 14 L/min, or more often between about 7 and 14 L/min. Flow rates that are too high or too low can result in losses in the amount of aerosolized medicament delivered to the proper locations of a user&#39;s respiratory system. An optimal inspiratory time may be between 6 and 24 seconds. Breathing indicator  116  can be used to direct a user to maintain an inhalation within these parameters. 
     The breathing indicator  116  may produce a different colored light as an “end of dose” indictor to indicate that substantially all of the dose of medicament has been delivered. For example, a blue light may be emitted for a period of time, such as between about 1 and 10 seconds to alert the user that substantially all of the dose has been aerosolized and inhaled. Delivery of the entire dose may be predefined as when at least about 95% of the dose is delivered, more preferably 98% and most preferably when more than 99% of the dose is aerosolized. To receive the dose, the user may take several inhalations or a single inhalation depending on the volume of liquid drug to be delivered and the user&#39;s breathing capacity. Each inhalation may be monitored by the device, with feedback provided to the user via indicator  116 , to insure proper delivery to the lungs. In some embodiments, the operation of the end of dose indicator may be delayed for a period, such as up to about 5 seconds after substantially all of the dose has been delivered, thus providing a “chaser” of air into the lungs. This chaser may serve to clear the upper airway and maximize the amount of the dose that is transported to the user&#39;s lungs. 
     In some embodiments, a cover  126  may be coupled with the fluid receiving chamber  114  and/or housing  108  to seal the fluid receiving chamber  114  and the vibratable mesh  112  when in a closed position. The cover  126  operates to prevent pathogens or other contaminants from entering the fluid receiving chamber  114 . The cover  126  may operate to expose the fluid receiving chamber  114  and vibratable mesh  112  when in an open position. Cover  126  may include a sliding mechanism (not shown) such that the cover  126  may be moved from an open position to a closed position and back by sliding the cover  126  within or on a track. In some embodiments, the cover  126  is hinged such that the cover  126  may be flipped open and closed. A latching mechanism (not shown) may be included to maintain cover  126  in a closed position. 
     In some embodiments, one or both of conduit  102  and aerosol generator  104  are removably coupled with housing  108 .  FIG. 3  shows an isometric view of aerosolization device  100  having conduit  102  and aerosol generator  104  removed from an opening  128  within housing  108 . Opening  128  may be configured to slidingly receive and secure one or both of conduit  102  and aerosol generator  104 . Power button  130  may be included to activate the aerosolization device  100 . Plug  124  may be positioned within opening  128  to couple the conduit  102  and/or aerosol generator  104  with the IC  138 . Male connector  144  of plug  124  can interface with female connector  146  of conduit  102 . 
       FIGS. 4A and 4B  show conduit  102  and aerosol generator  104  removed from housing  108 . Conduit  102  and aerosol generator  104  may be separate components and/or share and exterior housing  132 . The exterior housing  132  may be configured to slide into opening  128  of housing  108 . In some embodiments, the exterior housing  132  may include an electrical connector  142 , as shown in  FIG. 4B . Electrical connection  142  may couple with plug  124  as seen in  FIGS. 1A, 1B, and 3  to couple the conduit  102  and/or aerosol generator  104  to IC  138 . Electrical connection  142  can include a female or male connection and couple with a corresponding connection on the plug  124 . For example, female connector  146  may interface with male connector  144  of plug  124 . In this manner, the exterior housing  132 , aerosol generator  104 , and/or conduit  102  may be removed for replacement while the housing  108 , IC  138 , and other components may be reused. The electric and/or control components are often more expensive to replace than the exterior housing  132 , aerosol generator  104 , and/or conduit  102 , so such reuse provides a cost effective solution when some components need to be replaced. 
       FIG. 5  depicts an embodiment of a flow restrictor plate that may be positioned within a conduit, such as conduit  102  of  FIGS. 1, 1A, 2, and 4 . Restrictor plate  10  creates resistance to and limits airflow through a conduit while adding minimal to no length to a conduit. The restrictor plate  500  provides an increase in pressure differential that varies with inspiratory flow rates. This pressure differential exists between the conduit and outside of the conduit and/or atmospheric pressure such that as the user&#39;s inhalation force increases, the pressure differential drops to maintain a relatively constant flow rate within the conduit that stays in a desired flow rate range. In some embodiments, the pressure differential increases in a linear relationship with the flow rate as the user&#39;s inhalation force increases. Sensory feedback provided by sensors and/or indicator mechanisms, such as those described above, may allow the user to relate inspiratory pressure with the required flow rate required to operate the aerosol generator. Restrictor plate  500  defines a plurality of apertures  502  for air to pass through. Apertures  502  can be positioned around an outer periphery of the restrictor plate  500  such that air passing through the apertures forms a relatively laminar flow downstream of the restrictor plate  500 . Apertures  502  can be of any shape or size to create a relatively laminar flow. For example, apertures may be circular and have diameters ranging between about 0.5 mm to 1.5 mm. The size and pattern of the plurality of apertures  502  can prevent airflow through a solid center portion of the restrictor plate  500 , while allowing airflow through the apertures on the periphery thereof. 
       FIG. 6  illustrates a restrictor plate  600  positioned within a conduit  602  in accordance with embodiments of the invention. Restrictor plate  600  is disposed within the conduit between a pressure transducer  604  that is in fluid communication with an interior of the conduit and an aerosol generator  606 . The pressure transducer  604  monitors a pressure differential within the conduit  602  relative to outside of the conduit and/or atmospheric pressure. A processing unit or IC, such as IC  138  of  FIG. 1 , may execute software that converts the pressure reading to a flow rate throughout the conduit  602 . This flow rate may be used to determine when to activate the aerosol generator  606  to aerosolize a volume of liquid medicament. Restrictor plate  600  may have the characteristics of the restrictor plate  500  discussed above. Restrictor plate  600  creates a laminar flow upstream of the aerosol generator  606  such that the aerosolized medicament is deposited within the laminar flow and entrained within the laminar flow before the aerosolized medicament contacts a wall of the conduit  602  opposite of the aerosol generator  606 , in order to maximize the amount of medicament delivered to the user. 
       FIG. 7  is a laminar flow diagrams of airflow through conduit  602  and restrictor plate  600  having a structure similar to restrictor plate  500 . As airflow reaches restrictor plate  600 , the pressure differential is increased and a relatively laminar flow is created to contact aerosolized medicament. The laminar flow provides a consistent velocity field to deliver the aerosolized particles to the user&#39;s respiratory system in a consistent manner while minimizing impactive losses. Additionally, the laminar flow minimizes an amount of aerosolized medicament that may be deposited on a wall of the conduit. The aerosolized medicament is entrained in the laminar flow before the medicament contacts a wall opposite of the aerosol generator  606 . The entrained aerosolized medicament is then carried out of the conduit  602  to a user&#39;s respiratory system. 
       FIGS. 8A-8C  show an aerosolization device having a mouthpiece end angled at various angles to direct airflow into a user&#39;s respiratory system. Mouthpiece end angles may be set based on the volume of a dose, type of medicament to be delivered, and length and diameter of the conduit of an aerosolization device.  FIG. 8A  shows an aerosolization device  800  having a mouthpiece end  802  angled downward 15° relative to a horizontal plane.  FIG. 8B  shows aerosolization device  800  having mouthpiece end  802  parallel relative to a horizontal plane.  FIG. 8C  shows aerosolization device  800  having mouthpiece end  802  angled upward 15° relative to a horizontal plane. Other angles relative to a horizontal plane of up to 30° up or down relative to a horizontal plane may be used to maximize delivery of the medicament to the user&#39;s respiratory system. 
       FIG. 9  shows an aerosolization device  900  having an input device  902  coupled with a housing  904 . In some embodiments, input device  902  may be coupled with a conduit. Input device  902  is configured to receive an input from a user that sets parameters for an inspiratory flow determined by a pressure transducer (not shown) within the conduit. The input may be manually entered by a user, provided via wireless interface, provided via wired interface, such as universal serial bus (USB), or in any other manner. The parameters, which may include a flow rate, an inspiratory pressure, an inspiratory time, and the like, may be used to determine when an aerosol generator of the aerosolization device  900  are actuated, as well as to set ranges for indicator mechanisms (not shown) that direct the user on when and how to breath. An input device  902  may include a keyboard or similar interface, a barcode scanner or RFID reader to receive flow parameters from a user or a container or label of the medicament. Aerosolization device  900  may be configured similar to any of the aerosolization devices described herein, and may include the same or similar features. 
       FIG. 10  depicts a method  1000  of delivering an aerosolized medication to a user&#39;s respiratory system using the aerosolization devices described herein. The method may include sensing a state of a flow parameter of an inspiratory flow within a conduit at block  1002 . Sensing a state of a flow parameter may be done using sensors, such as a flow sensor or the pressure transducer  404  of  FIG. 4 . The method may also include vibrating a mesh of an aerosol generator in communication with the conduit to aerosolize a volume of a liquid medicament at block  1004 . This vibration produces a plume of aerosolized medicament within a conduit of the aerosolization device when a state of the flow parameter is within a predefined desired range. For example, when an inspiratory flow rate determined by the pressure transducer is within an operating range of the aerosolization device, the mesh may be vibrated. The plume of aerosolized medicament may be provided within a relatively laminar flow produced by a restrictor plate disposed within the conduit upstream of the plume of aerosolized medicament. The laminar flow sweeps the aerosolized medicament toward a mouthpiece end of the conduit before the medicament contacts a wall of the conduit opposite the aerosol generator. The aerosolized medicament is then directed into a user&#39;s respiratory system. 
     In some embodiments, the method may further include providing an indication using an indicator mechanism coupled with the conduit of the state of the flow parameter relative to the predefined desired range at block  1006 . In some embodiments, the method may further include providing an indication that the liquid medicament is ready to be aerosolized and providing an indication that substantially all of the liquid medicament has been aerosolized. The method may optionally include receiving an input via an input device of the aerosolization device to set the predefined desired range of the flow parameter. In some embodiments, the method may further include moving a cover that is coupled with the conduit to expose the chamber and vibratable mesh for receiving the liquid medicament. In some embodiments, the method may optionally include receiving a tip of a dispenser within the aerosol generator and receiving a volume of liquid medicament from the dispenser on the mesh. The tip may be maintained a distance above the mesh such that an outer surface of the tip does not contact the received volume of liquid medicament. In some embodiments, the method may also include attaching the conduit and aerosol generator to a housing. For example, the conduit and aerosol generator may be slid into and secured within an opening the housing. 
     EXPERIMENTAL EXAMPLE 
     Prevention of contamination due to a user coughing or sneezing into the conduit using an aerosolization device having a vibratable mesh that is laterally offset from an inner wall of the conduit as described in  FIGS. 1A and 1B , was simulated by spraying culture broth of five types of pathogens into the conduit using a 100 μl nasal spray pump. One spray was emitted from the primed nasal pump directly into an opening of the conduit. A 30 μl dose of saline was then nebulized using the aerosol generator to simulate the completion of a dose. The aerosolized saline was collected on a culture plate with medium specific to the pathogen testes. The contaminated aerosolization device was then allowed to sit in ambient conditions for 4 hours. Another dose of saline was then nebulized in the aerosolization device with the aerosolized saline again collected on a culture plate. All plates were incubated, with no pathogens found in the saline samples from either sample time. 
     It will be apparent to those skilled in the art that various modifications and variations can be made in the method and system of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention include modifications and variations that are within the scope of the appended claims and their equivalents.