Dry powder inhaler devices, multi-dose dry powder drug packages, control systems, and associated methods

Abstract

Dry powder inhalers with integrated active energy patient assist dispersal systems are configured with control systems which provide adjustable energy output responsive to the user's inspiratory capabilities and/or the flowability of the dry powder drug being administered. The multi-dose dry drug package includes a piezoelectric polymer substrate (such as PVDF) which flexes to deform and provide mechanical oscillation in a selected region of the package corresponding to the dry powder drug dose in the exit flow path and is thus actively dispersed into the exit flow path of the inhaler during the user's inspiratory activity. Control systems employ fuzzy logic models of the flowability of particular drug formulations (also being able to compensate or allow for the particular type of excipient used) and/or adjust for the real-time measured inspiratory efforts of the user. Manufacturing process control systems can adjust certain parameters in response to a fuzzy logic model of the flowability of the dry powder and other conditions associated with the dry powder drug being produced and/or dispensed.

1 . A multi-dose dry powder blister package, comprising: 
 a platform body comprising a piezoelectric material layer with opposing first and second major surfaces;    a first plurality of spatially separated metal traces disposed on said first major surface of said piezoelectric material layer, said first plurality of metal traces configured to include a transmission line and an active pad region;    a second plurality of spatially separated metal traces disposed on said second major surface of said piezoelectric material, said second plurality of metal traces configured to include a transmission line and an active pad region, each of said second plurality of traces being positioned such it is aligned with a corresponding one of said first plurality of separated metal traces to define a corresponding pair of opposing metal traces with an individually operable electrical excitation path therebetween; and    a plurality of depressed wells formed in said platform body configured to hold a predetermined quantity of dry powder pharmaceutical drug therein, wherein each of said depressed wells is positioned on said platform body to substantially overlie a respective active pad region of one pair of corresponding first and second metal traces.    
   
   
       2 . A multi-dose dry powder blister package according to  claim 1 , wherein, in operation, in response to application of an excitation voltage differential to a selected one of said individually operable electrical paths, said piezoelectric material layer deforms at said active pad region to thereby actively disperse said dry powder pharmaceutical drug from said depressed well.  
   
   
       3 . A multi-dose dry powder blister package according to  claim 1 , further comprising a sealed releasable polymer cap positioned to overlie said plurality of depressed wells.  
   
   
       4 . A multi-dose dry powder blister package according to  claim 3 , further comprising a non-reactive barrier positioned in each of said depressed wells to define a dry powder drug contact surface therein.  
   
   
       5 . A multi-dose dry powder blister package according to  claim 4 , further comprising a backing material layer positioned to overlie a substantial portion of said second major surface.  
   
   
       6 . A multi-dose dry powder blister package according to  claim 1 , wherein said piezoelectric material is a thin film PVDF.  
   
   
       7 . A multi-dose dry powder blister package according to  claim 6 , wherein said first and second pluralities of metal traces are configured substantially symmetrically about opposing sides of said thin film PVDF.  
   
   
       8 . A multi-dose dry powder blister package according to  claim 1 , wherein said dry powder pharmaceutical drug comprises active ingredient particulates having a size of about 0.5-8.0 μm.  
   
   
       9 . A multi-dose dry powder blister package according to  claim 8 , wherein said dry powder pharmaceutical drug comprises a flow enhancing ingredient having a particulate size which is greater that the active ingredient-particulates.  
   
   
       10 . A multi-dose dry powder blister package according to  claim 9 , wherein said flow enhancing ingredient includes particulates having a size of about 50-1100 μm.  
   
   
       11 . A multi-dose dry powder blister package according to  claim 10 , wherein said dry powder pharmaceutical drug flow enhancer ingredient comprises lactose.  
   
   
       12 . A multi-dose dry powder blister package according to  claim 2 , in combination with a power source, wherein a selected one of said pairs of metal traces in each of said individually operable electrical paths is configured to operate with positive polarity while the other is configured to operate as one of an opposing negative polarity or ground.  
   
   
       13 . A multi-dose dry powder blister package according to  claim 12 , wherein said power source is configured to supply an input voltage in the range of about 100-200 volts peak to peak to said individually operable electrical paths.  
   
   
       14 . A multi-dose dry powder blister package according to  claim 12 , wherein the excitation voltage is applied at a frequency of between about 3-60 Hz to facilitate a fluidized dispersion of said dry powder drug.  
   
   
       15 . A multi-dose dry powder blister package according to  claim 12 , wherein the excitation voltage is applied at a frequency of between about 25 kHz-2 MHz.  
   
   
       16 . A multi-dose dry powder blister package according to  claim 1 , wherein said platform body is substantially circular, and wherein said plurality of spaced apart metal traces are circumferentially spaced apart.  
   
   
       17 . A multi-dose dry powder blister package according to  claim 1 , wherein said platform body is substantially linear and has a length and width, and wherein said plurality of spaced apart metal traces are spaced apart along said platform body length.  
   
   
       18 . A multi-dose dry powder blister package according to  claim 17 , wherein said platform body is endless in the length direction, and wherein said transmission lines of said spaced apart metal traces extend in the width direction of said linear platform body.  
   
   
       19 . A multi-dose dry powder blister package according to  claim 1 , wherein said package is configured to be received in a dry powder inhaler, said dry powder inhaler comprising a housing and a control system located therein, wherein during operation, said housing is configured to be in fluid communication with a user and defines a flow exit path therefrom, said control system comprising: 
 a controller configured to engage with a selected one of said individually operable electrical excitation paths;    a battery having a first voltage output operably associated with said controller;    a transformer for increasing said first voltage to a desired excitation voltage operably associated with said controller and said selected individually operable electrical path; and    an air flow sensor positioned in said flow exit path.    
   
   
       20 . A multi-dose dry powder blister package according to  claim 19 , wherein said air flow sensor is positioned downstream of said depressed well in said flow exit path.  
   
   
       21 . A multi-dose dry powder blister package according to  claim 19 , wherein said controller is configured to adjust said excitation voltage corresponding to predetermined parameters associated with the dispersion of said dry powder drug.  
   
   
       22 . A multi-dose dry powder blister package according to  claim 21 , wherein said controller is programmed with a fuzzy logic system representing at least one of flow characteristics of said dry powder drug and the inspiratory capability of a user such that said controller controls the excitation voltage transmitted to said selected electrical path responsive to said fuzzy logic system.  
   
   
       23 . A disposable multi-dose dry powder package, with an integrated active element formed thereon, comprising: 
 a piezoelectric polymer film having a substantially planar profile and an upper and lower surface;    a first metal trace pattern positioned onto said upper surface, said first metal trace pattern having a plurality of first pad regions, and a plurality of first linear transmission lines, wherein said first pad region is connected to a respective one first linear transmission line;    a second metal trace pattern positioned onto said lower surface, said second metal trace pattern having a plurality of second pad regions, and a plurality of second linear transmission lines, wherein each second pad region is connected to a respective one second linear transmission line, and wherein said first and second metal trace patterns are aligned across said piezoelectric polymer material layer;    a plurality of individual quantities of dry powder drug positioned to substantially overlie each of said first pad regions on said upper surface; and    a sealant layer positioned to overlay each of said unitized quantities of dry powder drug to secure it in said disposable dry powder package.    
   
   
       24 . A multi-dose dry powder blister package according to  claim 23 , further comprising a non-reactive barrier positioned to overlie the upper surface of said first pad region to define a dry powder drug contact surface.  
   
   
       25 . A multi-dose dry powder blister package according to  claim 24 , further comprising a backing material layer positioned to overlie a substantial portion of the lower surface of said piezoelectric polymer film.  
   
   
       26 . A multi-dose dry powder blister package according to  claim 23 , wherein said piezoelectric polymer film is a thin film PVDF.  
   
   
       27 . A method of dispersing an inhalable quantity of a dry powder pharmaceutical drug to a patient's airstream, comprising the steps of: 
 positioning and holding a dry powder inhaler such that it is in fluid communication with a user and ready to direct a quantity of dry powder pharmaceutical drug into the airstream of a user during inhalation, wherein the package holds at least one unitized quantity of dry powder pharmaceutical drug in a receptacle portion of thereon, the receptacle portion including a piezoelectric polymer material layer;    repeatedly applying a voltage differential across the piezoelectric polymer film in the region of the receptacle to deform the receptacle; and    expelling the dry powder drug held in the receptacle portion of the package such that it is dispersed into the airstream of a user during the user's inspiratory inhalation cycle.    
   
   
       28 . A method according to  claim 27 , wherein said deforming step is carried out by flexing the piezoelectric material in the region of the receptacle portion.  
   
   
       29 . A method according to  claim 27 , wherein said applying step is carried out by providing a voltage of about 100-200 volts peak to peak.  
   
   
       30 . A method according to  claim 29 , wherein said applying step is carried out at a frequency of between about 3-60 Hz.  
   
   
       31 . A method according to  claim 30 , wherein said applying step is carried out at a frequency of between about 25 kHz-2 MHz.  
   
   
       32 . A method according to  claim 27 , further comprising the step of measuring the inspiratory air flow rate of a user.  
   
   
       33 . A method according to  claim 32 , wherein said method further comprises the steps of controlling the voltage applied during said applying step responsive to the user's inspiratory flow rate obtained from said measuring step.  
   
   
       34 . A method according to  claim 33 , wherein said measuring step is performed temporally proximate to active dispersion of the dry powder drug from the receptacle into the dry powder inhaler.  
   
   
       35 . A method according to  claim 27 , wherein the voltage applied in said applying step is automatically adjusted during active operation of the dry powder inhaler responsive to the inspiratory ability of the user.  
   
   
       36 . A method according to  claim 35 , further comprising the steps of: 
 defining a fuzzy logic function representing at least one predetermined condition, said at least one condition associated with at least one of the configuration of the dry powder inhaler, the inspiratory ability of the user, flowability of the formulation of the dry powder pharmaceutical drug being administered, and respirable particle fraction data associated with dry powder formulation;    determining the degree of membership for said at least one condition to said defined fuzzy logic function; and    adjusting the excitation voltage applied during said applying step based on said defining and determining steps.    
   
   
       37 . A method according to  claim 36 , wherein said fuzzy logic function controls the voltage output delivered during said applying step, and wherein said fuzzy logic function is defined to represent at least two conditions, the at least two conditions corresponding to at least two of the flowability of the formulation of the dry powder pharmaceutical drug, the presence and characteristics of any excipient used therein, the geometry of the dry powder inhaler, and a measured airflow rate corresponding to the inspiratory ability of the user.  
   
   
       38 . A method according to  claim 27 , further comprising the steps of programming the dry powder inhaler with a computer readable program code which identifies a range of operational excitation output pulses having associated frequencies, amplitudes, and signal patterns associated therewith, and programming into the dry powder inhaler with computer readable code which defines operational excitation output pulses suitable for predetermined types of dry powder drug formulations.  
   
   
       39 . A method according to  claim 38 , further comprising the step of programming the dry powder inhaler with a computer readable program which provides a range of desired operational excitation pulses for particular types of systemic delivery targets.  
   
   
       40 . A method according to  claim 27 , wherein the piezoelectric polymer film is PVDF.  
   
   
       41 . A method of facilitating the dispersion of a dose of a dry powder drug into an inhalation delivery path, comprising the steps of: 
 positioning a quantity of dry powder drug in a package having an piezoelectric polymer material layer, the piezoelectric polymer material layer having a plurality of receptacle regions configured and sized to hold the dry powder drug proximate thereto, the piezoelectric polymer material layer configured with a plurality of selectively excitable regions corresponding to the plurality of receptacle regions;    selectively applying an excitation signal to at least one of the selectively excitable regions to rapidly flex the piezoelectric polymer material layer thereat to deform at least one receptacle region to thereby facilitate the dispersal of the dry powder drug into the inhalation delivery path.    
   
   
       42 . A method according to  claim 41 , wherein the piezoelectric polymer film is PVDF.  
   
   
       43 . A method according to  claim 41 , wherein said applying step is carried out by providing an input voltage across said piezoelectric polymer material in the region of at least one of said plurality of receptacles of about 100-200 volts peak to peak.  
   
   
       44 . A method according to  claim 41 , wherein said excitation signal is applied at a frequency of between about 3-60 Hz.  
   
   
       45 . A method according to  claim 41 , wherein said excitation signal is applied at a frequency of between about 25 kHz-2 MHz.  
   
   
       46 . A method of controlling a dry powder inhaler, comprising the steps of: 
 providing a dry powder inhaler having an active delivery system and an air flow sensor positioned in the exit flow path;    measuring the air flow associated with the inspiratory efforts of a user using the dry powder inhaler proximate to the desired administration of the dry powder drug; and    adjusting the energy directed to the active delivery system responsive to said measuring step to thereby facilitate increased dose dispersion uniformity corresponding to the capabilities of a user.    
   
   
       47 . A method of fabricating a disposable multi-dose dry powder package having integrated active elements formed thereon, comprising the steps of: 
 forming a package with at least one piezoelectric polymer film layer into a desired geometric shape with an upper and lower surface;    dispensing a quantity of dry powder drug to substantially overlie a plurality of spatially separate selected upper surface regions of the piezoelectric polymer film layer; and    sealing said dispensed dry powder drug to secure it against the dry powder package.    
   
   
       48 . A method according to  claim 47 , wherein said at least one piezoelectric polymer film layer is one film layer, said method further comprising: 
 forming a first metal trace pattern onto the upper surface, the first metal trace pattern having a plurality of pad regions, and a plurality of linear transmission lines, a respective one connected to each of said pad regions; and    forming a second metal trace pattern onto the lower surface, the second metal trace pattern having a plurality of pad regions, and a plurality of linear transmission lines, a respective one connected to each of said pad regions;    
   
   
       49 . A method according to  claim 47 , wherein said at least one piezoelectric polymer film layer is, two layers separated by an intermediately positioned pliable core.