Abstract:
A dry powder delivery device may be configured to provide micronized dry powder particles to airways of a user. The device may include a cylindrical container delimiting a chamber containing at least one magnetically-responsive object, a motor external to said chamber, a magnet external to the chamber and rotatably coupled with the motor, and an outflow member configured to direct airflow to a user. The magnetically-responsive object may be coated with micronized dry powder particles, and the motor may be operable to rotate the magnet about an axis. Rotation of the magnet creates a magnetic field that causes the magnetically-responsive object to move in response to the magnetic field and collide with a side wall of the container to deaggregate the dry powder particles and aerosolize the dry powder in the chamber.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of priority of U.S. provisional application No. 61/311,707, entitled “Dry Powder Nebulizer,” filed on Mar. 8, 2010, and U.S. provisional application No. 61/456,812, entitled “Dry Powder Nebulizer,” filed on Nov. 12, 2010, the contents of both of which are incorporated herein by reference. 
     
    
     TECHNICAL FIELD 
       [0002]    The present disclosure relates to systems and methods of delivering micronized dry powder particles to the airways of a patient and, more particularly, a dry powder nebulizer and method for delivering micronized drug powder particles to the deep lung of a patient. 
       BACKGROUND 
       [0003]    Technological advancement in the context of targeted drug delivery to the lung continues to be an emerging field. The ability to deliver therapeutic agents specifically to the lung has been popular in the treatment of specific disease states such as asthma, chronic obstructive pulmonary disease (COPD), infections, cancer, and others. Given its extremely large surface area, mild environment, and ease of administration, in contrast to oral and intravenous routes of drug delivery, the lung presents an especially attractive avenue of therapeutic delivery. 
         [0004]    However, pulmonary drug delivery is not without its obstacles. For drug particles to deposit in the deep lung, where they exert their therapeutic action, they must possess certain physical properties. Specifically, the drug particles must have an aerodynamic diameter below 5 microns, where the aerodynamic diameter encompasses both the density and geometric diameter of the drug particle. Accordingly, aerosolized drug particles must be less than 5 microns in aerodynamic diameter when they exit an inhaler to deposit in the deep lung. 
         [0005]    The majority of devices for targeted drug delivery to the lung can be categorized into one of three groups: metered dose inhalers (MDI), dry powdered inhalers (DPI), and nebulizers. Researchers have advanced each technology to more adequately fit the needs of prescribers, patients, and even environmentalists concerned with the release of ozone-depleting propellants. While many of the devices currently utilized in theory deliver a set dose, patient variables such as inspiratory capacity and coordination alter the performance and thus therapeutic effect achieved through the use of the device. Most devices however, deliver only small quantities of drug per dose or take long periods of time to deliver a clinically relevant dose in many diseases. 
         [0006]    Metered-dose inhalers consist of a small device which contains a formulation of drug particles suspended in a liquid. Typically the doses delivered by these inhalers are small, in the microgram range, often too small for many clinical applications. The patient can then actuate the device to receive a set, metered, dose. Although these devices do not require a significant inspiratory capacity (30 L/min, e.g.), they do require the patient to have been properly counseled and demonstrate consistent coordination to receive the intended manufacturers&#39; dose. Although spacers and other devices have been developed to circumvent this problem, many patients continue to inappropriately utilize their devices, compromising the effectiveness of their medication and leading to poorer and unpredictable patient outcomes. Formulation problems such as the inability to include drugs not stable in a liquid environment and a limited shelf-life are also major challenges. Further, propellants which used to be included in many formulations to assist in the delivery process, such as chlorofluorocarbons (CFCs), have been suspect in the depletion of the ozone layer and manufacturers have been required to reformulate their products to contain non-hazardous materials. This change has led to patients having to change their products, which are potentially more expensive and inconsistent in therapeutic efficacy. 
         [0007]    Traditional nebulizers are also liquid formulations of drugs which are delivered to patients who cannot physically actuate or coordinate MDIs or DPIs, primarily young children and the very ill. They carry many of the same formulation and stability problems as MDIs and additionally are inefficient, bulky, and require the patient to breathe the contents over lengthy periods of time (15-30 minutes) due to the need to dissolve or finely disperse the drug within an aqueous liquid. As many medications used to treat disease states are prescribed to be taken several times a day, using nebulizers remain an inconvenience to patients and caretakers particularly due to these long treatment times. 
         [0008]    Dry powdered inhalers can be broken down into two sub-categories, passive and active devices. DPIs are formulations of dry powders which are administered at set doses. Currently, the majority of DPIs on the market are passive, meaning they are designed to deliver their intended dose when the patient has demonstrated a significant inspiratory capacity (60 L/min, e.g.) needed to mobilize the powders. Although DPIs are free from many of the issues and concerns that restrict MDIs and nebulizers (such as formulation, stability, coordination, and hazardous complications), their performance, and corresponding drug delivery, can be drastically impaired if the patient is unable to inspire at the tested rate; common in COPD, asthma, and pediatric populations. This, again, can lead to unpredictable and unfavorable patient outcomes if used incorrectly. For example, DPI&#39;s currently on the market are inadequate because they are liquid formulations, which result in instability, incompatibility, a requirement of advanced coordination, and provide erratic delivery, which in heightened with improper use. Furthermore, the current dry powder formulations have limited delivery and require large inspiratory force, adversely affecting the sick, elderly, and children. This has shown to be problematic for patient populations who have diminished lung function resulting from advanced age or the disease process itself. These populations might experience more therapeutic failures and adverse effects related to the drug due to inability to generate a dispersion patter reflective of those seen in clinical trials. 
         [0009]    In an attempt to mitigate this unpredictability, research groups have focused on developing active devices. Active devices utilize a power source to decrease the need for the patient to inspire at the typical DPI requirement, however, many of these devices have not yet come to market and may demonstrate some dosing inconsistencies when used at different patient inspiratory flow rates. In addition, many devices are exceedingly complicated in design and manufacture, adding time and cost to the development of therapies. DPIs can deliver a wide range of doses from low micrograms to milligrams. Having the drug in the solid state enables higher payloads than if the drug needs to be dispersed or dissolved in a solvent. However, as the doses increase, generally performance decreases. 
         [0010]    Another caveat for targeted drug therapy is payload capabilities. When considering drug classes such as aminoglycosides and fluoroquinolones, the effectiveness of therapy is dependent on the amount of drug exposed to the site of interest. 
         [0011]    It may be desirable to provide a drug delivery device incorporating many of the beneficial qualities of the above MDI, DPI, and nebulizer devices as well as additional features which have the potential to benefit several disease states, unique from the other devices currently on the market. It may be desirable to provide consistency in the delivery of relatively large doses and intermediate doses under conditions which model inter- and intra-patient variability have historically created problems in the performance for standard devices. It may be desirable to provide a device that offers high doses and excellent performance at various flow rates and various orientations (as patients will position the device differently each time they use) and aesthetic appeal. Finally, it may be desirable that the device is simple and cost minimized. 
       SUMMARY OF INVENTION 
       [0012]    According to various aspects of the disclosure, a dry powder delivery device may be configured to provide micronized dry powder particles to airways of a user. The device may include a cylindrical container delimiting a chamber containing at least one magnetically-responsive object, a motor external to said chamber, a magnet external to the chamber and rotatably coupled with the motor, and an outflow member configured to direct airflow to a user. The magnetically-responsive object may be coated with micronized dry powder particles, and the motor may be operable to rotate the magnet about an axis. Rotation of the magnet creates a magnetic field that causes the magnetically-responsive object to move in response to the magnetic field and collide with a side wall of the container to deaggregate the dry powder particles and aerosolize the dry powder in the chamber. 
         [0013]    According to some aspects, the magnetically-responsive object may comprise a magnet such as, for example, a Teflon-coated magnet. In some aspects, the magnetically-responsive object may comprise a capsule containing a magnetically-responsive member. The capsule may comprise a polymer. 
         [0014]    In accordance with various aspects of the disclosure, a method of delivering micronized dry powder particles to a patient may include rotating a magnet exterior to a chamber to create a magnetic field that causes responsive movement of at least one magnetically-responsive object coated with micronized dry powder particles and contained in the chamber, deaggregates the micronized dry powder particles from the magnetically-responsive object, and aerosolizes the deaggregated particles in the chamber. The method further includes directing a flow of air including the aerosolized particles from the chamber to an outflow member. 
         [0015]    In some aspects, the rotating step begins in response to patient activation, which may include inhalation at a mouthpiece coupled with an outflow member of the container. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]      FIG. 1  is a perspective view of an exemplary dry powder nebulizer in accordance with various aspects of the disclosure. 
           [0017]      FIG. 2  is a perspective view of an exemplary dry powder nebulizer in accordance with various aspects of the disclosure. 
           [0018]      FIG. 3  is a perspective view of an exemplary dry powder nebulizer in accordance with various aspects of the disclosure. 
           [0019]      FIG. 4  is a graph illustrating performance measures of an exemplary nebulizer using ciprofloxacin drug particles. 
           [0020]      FIG. 5  is a graph illustrating the quantity (mg) of ciprofloxacin delivered to the “in vitro deep lung” by an exemplary nebulizer. 
           [0021]      FIG. 6  is a graph illustrating the percentage of ciprofloxacin distributed in various components of a model airway system and an exemplary nebulizer. 
       
    
    
     DETAILED DESCRIPTION 
       [0022]      FIGS. 1 and 2  illustrate a diagrammatic perspective view of a drug delivery device comprising an exemplary dry powder nebulizer assembly  100  according to various aspects of the disclosure. The dry powder nebulizer assembly  100  includes a container  102  having a top wall  104 , a bottom wall  106 , and at least one side wall  108  extending between the top and bottom walls  104 ,  106 . The top wall  104 , bottom wall  106 , and side wall  108  cooperate to delimit a dosing chamber  110 . According to various aspects, the bottom wall  106  may be pounded out so as to form an uneven, bumpy inner bottom surface of the dosing chamber  110 . The effect of the uneven bottom surface is discussed in more detail below. 
         [0023]    According to some aspects, the container  102  may comprise a container such as, for example, a cylindrical aluminum canister. It should be appreciated that the container may comprise a metal, a polymer, or a combination thereof as long as it is not a paramagnetic material. In some aspects, a low static material that does not triboelectrify may be desirable. In some embodiments, the cylindrical canister may measure about 1.5 to 3 inches in height, for example, about 2.25 inches. In some aspects, the cylindrical canister may taper from the bottom wall  106  to top wall  104 . For example, in one exemplary embodiment, the canister may taper from a diameter of about 0.875 inches at the bottom wall  106  to about 0.7 inches at the top wall  104 . According to various embodiments, the diameter at the bottom wall  106  of the canister may range from 0.7 to 1 inch, and the diameter at the top wall  104  of the canister may range from about 0.5 to 0.8 inches. It should be appreciated that these ranges are exemplary only and may be lesser or greater depending on the user&#39;s desired parameters. 
         [0024]    The container  102  may include one or more air inlets  112  in the side wall  108 . According to some aspects, the container  102  may include two air inlets  112  provided via hollow shafts  114  disposed at opposite sides of the container  102  relative to one another. The shafts  114  extend outward from the container  102  in directions opposite to one another. 
         [0025]    The container  102  contains a magnetically responsive object. Referring to  FIG. 1 , according to some aspects, the container  102  may contain at least one miniature magnet  120  in the dosing chamber  110 . The at least one magnet  120  may comprise, for example, a plurality of micron-sized, polymer-coated magnets or magnetically-responsive beads. The number, weight, and size of magnets  120  may vary according to the size of the container  102 , the desired dosing, and other design parameters. In some aspects, the magnets  120  may range from about 300 μg to about 1 mg in weight. In some embodiments, the magnets  120  may have a length from about 0.35 to 0.4 inches, a width of about 0.1 to 0.15 inches, and a thickness of about 0.1 to 0.15 inches. For example, the magnets  120  may have a length of about 0.375 inches, a width of about 0.125 inches, and a thickness of about 0.125 inches. It should be appreciated that the aforementioned ranges are exemplary only and may be lesser or greater depending on the user&#39;s desired parameters. According to some aspects, for example, the magnet(s) or bead(s) may comprise a Teflon-coated magnet(s) or bead(s). Further, the polymer-coated magnet(s) or bead(s) includes a desired drug coated thereon. 
         [0026]    Referring now to  FIG. 2 , in some aspects, a nebulizer assembly may include a container  102  containing at least one capsule  220 . In some aspects, the capsule  220  may comprise a polymer or a polymer coating, such as, for example, Teflon. Each capsule  220  contains a pre-measured amount of drug powder and at least one miniature magnet  222 . In some aspects, each magnet  222  may comprise a stir bar or a neodymium magnet, for example. The magnet(s)  222  help to weigh down the capsule(s)  220  such that gravity keeps the capsule(s) toward the bottom wall  106  of the container  102  in the dosing chamber  110 . 
         [0027]    Referring again to  FIG. 1 , the nebulizer assembly  100  further includes a motor  150  external to the container  102 . The motor  150  may comprise a small conventional rotational motor, such as for example a motor used in toys and the like. The motor  150  may have a lower power requirement such that one or more small button-type batteries, for example three hearing air type batteries, may be employed as a power source and may be contained in a housing associated with the motor. In some embodiments, the motor may operate at approximately 1800 to 2200 revolutions per minute. According to some aspects, the motor  150  may be powered by an ac power source. 
         [0028]    The motor  150  may include a magnet  152  coupled with the output shaft  154  of the motor  150  so as to rotate therewith. The magnet  152  may comprise a rare earth magnet such as, for example, a neodymium magnet. In some aspects, the magnet  152  may be cylindrical; however, it should be understood that other shapes of magnets may be used depending on the user&#39;s desired parameters. It should be appreciate that any other types of magnets and/or magnetic materials may be utilized. Generally, a stronger external magnet  152  may be used if the internal magnets  120 ,  222  are weaker, and a weaker external magnet  152  may be used if the internal magnets  120 ,  222  are stronger. The size of the magnet may vary based on the need to create a magnetic field sufficient to influence movement of the magnets  120  or capsules  220  contained in the dosing chamber  110  of the container  102  when the magnet  152  is placed in proximal relation to an outer surface  140  of the bottom wall  106  of the container  102 . According to various aspects, the nebulizer  100  may be activated when the motor  150  is activated via a patient-operated control switch (not shown). In some aspects, the nebulizer  100  may be activated when a patient inhales at the mouthpiece, as would be understood by persons skilled in the art. 
         [0029]    The nebulizer assembly  100  further includes an outflow member  160  for delivering air containing aerosolized drug particles to a patient. In some aspects, the outflow member  160  may comprise a conduit, for example, rubber tubing coupled at one end to the top wall  104  of the container  102  in an airtight relationship. A second, opposite end of the outflow member  160  may form a mouthpiece  162  configured for insertion into a patient&#39;s mouth during an inhalation procedure. In some aspects, a separate mouthpiece (not shown) may be coupled with the outflow member  160 . In various aspects, the outflow member  160  and/or mouthpiece may be removable from the assembly  100  and/or disposable. In some aspects, the tubing may measure approximately 0.8 inches in diameter and 6 inches length. 
         [0030]    The outflow member  160  may contain a filtering member  164  such as, for example, a mesh for preventing undesired particulate from exiting the nebulizer assembly  100  via the mouthpiece  162  and entering a patient&#39;s airways. According to some embodiments, the filtering member  164  may comprise non-paramagnetic wiring woven and incorporated in the outflow member  160  to create a mesh to prevent unwanted particulate from entering the airways. The container  102  may include an inlet hole  170  for dilution air during breathing/inhalation by the patient. 
         [0031]      FIG. 3  illustrates a perspective view of an exemplary dry powder nebulizer  300  according to the disclosure. The nebulizer  300  is similar to the exemplary nebulizer  100  described above. However, in the nebulizer  300 , the airflow inlets  312  comprise holes  314  in the side wall  308  of the container  302 .  FIG. 3  illustrates the holes  314  on opposing regions of the side wall  308  proximate a bottom wall  306  of the container  302 . However, it should be appreciated that the holes  314  may be disposed at other locations along the side wall  308  between the bottom wall  306  and a top wall  304 . 
         [0032]    In operation, the nebulizer  100 ,  300  may be activated via patient-operated switch that activates the motor. Additionally or alternatively, the nebulizer may be activated when a patient inhales at the mouthpiece, as would be understood by persons skilled in the art. Once the nebulizer  100 ,  300  is activated, the motor and associated magnet turn and generate a magnetic field. The substantially constant revolution and resulting magnetic field cause the magnets or capsules in the dosing chamber to continuously collide with the side wall of the dosing chamber. The drug-coated magnet(s)  120  or capsule(s)  220  containing drug powder displays a chaotic movement directed by the influence of changing magnetic fields induced by the external magnet/motor and the internal shape of the dosing/holding chamber that causes collisions and forces of deaggregation for the drug-coated internal magnet/bead. This force disperses the deaggregated drug into a “cloud” which can then be inhaled by the patient over a set period of time. 
         [0033]    The uneven inner surface of the bottom wall of the container facilitates the collisions between the magnets or capsules and the side wall. The airflow inlets extending tangentially from the side wall of the container proximal the bottom wall help to create an upward cyclonic push of air during activation of the motor. Such upward cyclonic push may improve the aerosolization of the drug powders and reduce the amount of drug which adheres to the inner surface of the side wall of the container, thereby improving efficiency of the nebulizer. 
         [0034]    The dosing chamber may include an inlet hole for dilution air during breathing/inhalation by the patient. The inhalation aerosol may be directed from the dosing chamber to the mouthpiece via the outflow member or other conduit. According to various aspects, the nebulizer may include a mesh, screen, filter, or the like positioned in the path of airflow from the dosing chamber to the mouthpiece so as to prevent the magnet(s) or bead(s) from leaving the chamber and reaching the patient. 
         [0035]    Regarding exemplary embodiments including capsules contained in the dosing chamber of the container, the capsules may contain a pre-measured amount of micronized drug powder encapsulated therein. The capsules include at least one hole sized such that once the nebulizer is activated, drug can be released via the at least one hole as the capsules are moved about and collide with the side wall and/or with one another in the dosing chamber. 
         [0036]    In some aspects, the capsule may be pierced to form one or more holes immediately prior to use. For example, the ends of the capsule can be pierced with 1-3 pin-sized holes on one or both sides. In some aspects, the capsule may have as few as one hole and as many as six or more holes, for example. It should be appreciated that the number and size of the holes may vary depending on the desired performance of the nebulizer. Persons skilled in the art would understand that the exemplary nebulizers may include a piercer (not shown) associated therewith. A user may squeeze a region of the nebulizer to cause the piercer to pierce the capsule as would be understood by persons skilled in the art. 
         [0037]    Regarding exemplary embodiments including a drug-coated micron-sized magnet or magnetically-responsive bead, drug powders may be loaded onto the micron-sized carrier magnets or bead, for example, by affixing a small spherical canister with loose drug and magnets/beads inside to a slow rotating motor (e.g., as would be seen in a low-tech tape recorder). The magnets/beads are thereby coated with multiple layers of drug powder. It should be appreciated that any method of coating magnets/beads is contemplated by and consistent with the present disclosure. 
         [0038]    It should be appreciated that nebulizers consistent with the present disclosure may provide customized medication delivery for patients. It should also be appreciated that any medication, drug, therapeutic, or other treatment particle desired to be delivered to a patient&#39;s airways is contemplated by the present disclosure. For example, the amounts (0.5 mg to several milligrams) and types of drug powders (antibiotics, long-acting beta agonists, steroids, immunosuppressives, etc.) could potentially be varied for patients and compounded based on standardized modeling of performance. By doing so, the nebulizer can be tailored to a patient&#39;s individual needs. For example, patients might need several antibiotics for treatment of cystic fibrosis, etc., and nebulizers consistent with the present disclosure might be able to provide all of them to a patient in one treatment. It should be appreciated that treatments can also be adjusted as the patient&#39;s needs change by simply compounding the capsules/carriers differently. 
         [0039]    It should be appreciated that nebulizers consistent with the present disclosure may provide one or more advantages such as increased efficiency, improved stabilization, ease of use, predictable delivery of medication, and reproducible delivery. Regarding increased efficiency, a substantial amount of drug may be delivered over seconds (as compared to 15-20 minutes with a traditional nebulizer) without the need of a bulky power source. Dry powder formulations may provide improved stabilization because such medications are less likely to degrade and dosing can be easily adjusted for each patient. 
         [0040]    It should be appreciated that nebulizers of the present disclosure do not require the coordination needed with conventional metered dose inhalers, nor do they require the inspiratory capacity needed to sufficiently activate a traditional dry powder inhaler. The power source used to activate the motor may comprise three conventionally-available hearing aid batteries, and the overall size of the device may be small enough to fit in a purse or small carrying device. 
         [0041]    It should be appreciated that nebulizers of the present disclosure may deliver a predictable amount of micronized drug to the “in vitro deep lung” which suggests a patient will receive his/her intended dose in the desired portion of their airway system. Delivery to the patient may also be reproducible despite variations in inspiratory capacity. Tests have shown that the dispersion of the micronized powders remains substantially consistent for airflow rates at 30 L/min and 60 L/min. Therefore, as a patient&#39;s lung function changes from day to day (depending on the control of their condition, illness, fatigue, etc.) the same dose can be delivered. 
         [0042]    Dispersion studies have been performed using a Next Generation Impactor (NGI), a device designed to model particle deposition in the human airways. The NGI consists of several components to replicate the mouth, neck, and various sub-fractions of the lung. Tracking how the drug disperses in the various compartments is necessary to predict the proportion of drug swallowed versus inhaled (a measure to predict side effects and systemic absorption through the gastrointestinal tract), drug remaining in the device, and drug which reached the target—the deep lung. Data analysis includes a series of efficiency measures (fine particle fraction (FPF), respiratory fraction (RF), and the fine particle dose (FPD)). These parameters are applicable when estimating the potential costs associated with the device as well as dosing limitations and side effects. 
         [0043]    The device has shown to be more efficient (relative to other devices on the market) and consistent in the delivery of our model drug, ciprofloxacin, at a relatively low inspiratory flow rate of 30 L/min for powder based systems. The majority of the drug that enters the body reaches the deep lung, which is a desirable trait when considering targeted drug therapy. Further, upon observation, our device seems to be rather consistent in delivery despite positioning changes. Our inhaler also has the ability to deliver large doses of drug over 15-30 seconds at 30 L/min, while maintaining a significantly improved efficiency compared to those on the market. This may have profound applications in a number of diseases. For example, fungal infections of the lung, especially in neutropenic patients who typically require fungicidal activity. 
         [0044]    Fungal infections of the lung most commonly involve  candida  and  aspergillus  organisms. Many of these organisms have become resistant to the anti-fungal azole class, and neutropenic patients often require prolonged hospitalization and intravenous formulations of amphotericin B or drugs within the echinocandin class, leading to skyrocketing healthcare costs. In addition to these organisms, other pathogens such as  cryptococcus  continue to surface and pose mortality threats as well as increased costs. Thus, formulations of amphotericin B and/or caspofungin (or another from the echinocandin class) complex for use in our device would have significant advantages in therapeutics. This novel and effective method to effectively treat primary fungal infections may achieve substantially improved patient outcomes (mortality) and cost-effectiveness. 
         [0045]    In addition to fungal infections, this technology has the potential to target other disease states of the lung where large quantities of drug are desired but where the patient lacks the ability to utilize other current methods. Moreover, delivery of high doses of drugs delivered to the lung for the purposes of systemic absorption is an attractive application and embodiment of the technology. 
       Example 
       [0046]    Method: 
         [0047]    Ciprofloxacin drug particles were jet-milled to micronized drug particles and loaded onto micron-sized, polymer coated magnets using a custom made tumbling apparatus. 
         [0048]    Trials to establish dispersion patterns were conducted using 2 drug-loaded magnets. Payload capability data was generated using 4 drug-coated magnets. 
         [0049]    A custom-made nebulizer device was assembled and comprised a neodynium magnet fixed upon a handheld, patient-operated, motor-driven rotating element external to a chamber where the drug-coated magnets were held. Upon activation of the motor, the rotation of the external magnet created a dynamic movement of the drug-coated magnets through magnetic field changes within the chamber (created by the rotating external magnet), which led to the production of an aerosolized drug cloud in the container. The outflow conduit of the container was fluidly coupled to a model airway system so that the aerosolized drug was then able to be drawn into the model airway system to assess performance. 
         [0050]    All studies were conducted using a Next Generation Impactor (NGI®) at 30 L/min for 30 seconds. The NGI® is an in vitro model of the human upper airways and lungs designed to predict particle deposition in the human airways. Concentrations in each component of the device and NGI were determined via UV absorbance at 480 nm, from which aerosol distribution patterns were calculated. Typical efficiency and performance measures, fine-particle fraction (FPF), respirable fraction (RF), and fine-particle dose (FPD), were subsequently calculated. 
         [0051]    As used throughout this disclosure, fine-particle fraction refers to the amount (%) of drug delivered to the deep lung (trays  3 - 8  of the NGI) relative to the amount of drug delivered to the body (mouth, throat, lung (i.e., mouth, ps, and trays  1 - 8 )). The respirable fraction (RF) refers to the amount (%) of drug delivered to the deep lung (trays  3 - 8  of the NGI) relative to the starting dose. The fine particle density (FPD) refers to the amount of drug (micrograms) which penetrate the deep lung (trays  3 - 8  of the NGI). 
         [0052]    Results: 
         [0053]    Using 2 drug-coated magnets, an average fine-particle fraction (FPF) and respirable fraction (RF) of 75% and 29%, respectively, was achieved and an average dose of 950 micrograms was delivered to the “in vitro deep lung” of the NGI.  FIG. 4  illustrates the performance measures of a device using ciprofloxacin. Fine particle fraction is the proportion of drug that reached the “in vitro deep lung” relative to the total amount which entered the NGI. Respirable fraction is the proportion of drug that reached the “in vitro deep lung” relative to the full dose. That is, respirable fraction accounts for drug which remained in the nebulizer device and NGI. 
         [0054]    When 4 drug-coated magnets were employed, greater than 4.4 milligrams of ciprofloxacin was delivered to the “in vitro deep lung” of the NGI, however the overall efficiency of the set-up was reduced (FPF=48%, RF=17%), as illustrated in  FIGS. 4 and 5 .  FIG. 6  illustrates the percentage of ciprofloxacin distributed in various components of the model airway system (i.e., NGI) and the nebulizer device. 
         [0055]    It can be concluded that the low inspiratory capacity needed to generate the deposition patterns observed may be advantageous when considering patient populations who have compromised lung function. The high payload capabilities present opportunities to exploit new targeted therapeutic strategies. 
         [0056]    It is noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless otherwise expressly and unequivocally limited to one referent. Thus, for example, reference to “a nebulizer” includes two or more different nebulizers. As used herein, the term “include” and its grammatical variants are intended to be non-limiting, such that the recitation of items in a list is not to the exclusion of other like items that can be substituted or other items that can be added to the listed items. 
         [0057]    It will be apparent to those skilled in the art that various modifications and variations can be made to the systems and methods of the present disclosure without departing from the scope of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.