Abstract:
An inhaler device for administration of a dry powder to a patient includes a package containing a dose of the dry powder and a magnetic field generator, which produces a magnetic field in a vicinity of the package. The magnetic field causes motion of particles of the powder so as to deaggregate the powder in the package, whereby the powder is inhaled by the patient. Preferably, the package includes walls made of a flexible material, which vibrate under the influence of the magnetic field so as to impart the motion to the particles.

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to drug delivery devices, and specifically to devices and methods for delivery of drugs by inhalation. 
     BACKGROUND OF THE INVENTION 
     Drug delivery by inhalation is well known in the treatment of respiratory disorders, such as asthma. Inhalation has also found use in delivery of systemic drugs through the lungs, wherein the drugs are absorbed directly into the blood stream without having to pass through (and be broken down by) the digestive tract. 
     Ultra-fine, dry powders, also known as micro- and nano-powders, are the subject of increasing interest in pharmaceutical manufacturing, because they provide a solution to many of the shortcomings of blended drugs. Active drug ingredients are produced, packaged and administered to the patient as pure, dry powders, without blending them with solvents or other agents. Elimination of the blending steps simplifies the manufacturing process, reduces development and manufacturing costs, makes dosage more accurate, and extends the drug&#39;s shelf life. 
     Dry powder inhalers are known in the art, for delivery of dry powder medications to the lungs. For optimal penetration and absorption in the lungs, the powder particles should be particularly fine—on the order of 4 μm in size, or less. The drawback of such ultra-fine, dry powders is that they are difficult to handle, tending to clump and stick in storage and to scatter when disturbed by even slight air movements. These handling problems must be overcome if dry powder drugs are to be used efficiently and safely, and special methods must be used for accurate dose processing and administration. 
     PCT patent publications WO 97/47346 and WO 97/47347, which are incorporated herein by reference, describe inhaler apparatus for use with fine powders. A dry powder inside the inhaler apparatus initially adheres to a substrate surface therein. When a patient using the apparatus inhales, an electrostatic field is triggered inside the inhaler. The field causes the powder to be lifted from the surface and drawn into the patient&#39;s mouth. To be handled in this manner, the powder must be pre-charged. For practical field intensities (in a hand-held device that is inserted in the patient&#39;s mouth), the amount of powder that can be delivered is limited. Furthermore, application of the field must be precisely timed relative to the patient&#39;s inhalation to avoid scattering the powder, and the air flow trigger required for this purpose is costly and complex. 
     MicroDose Technologies Inc., of New Jersey, offers a dry powder inhaler based on the general principles described in the above-mentioned PCT publications. In addition to the used of a timed electrostatic field, the MicroDose inhaler uses a piezoelectric vibrator, brought into contact with a blister pack containing the powder, to deaggregate the particles. The mechanical interface for transferring the vibrations to the powder in the pack is inefficient and further increases the cost and complexity of the inhaler. 
     SUMMARY OF THE INVENTION 
     It is an object of the present invention to provide improved devices and methods for delivery of dry powders to a patient by inhalation. 
     It is a further object of some aspects of the present invention to provide a dry powder inhaler device that deaggregates the powder without the need for a direct mechanical interface to transfer vibrations to a package containing the powder. 
     It is yet a further object of some aspects of the present invention to provide a dry powder inhaler device from which the powder is released during inhalation by a patient using of the device, without the need for an air flow sensor or other means of active synchronization with the patient&#39;s respiration. 
     It is still a further object of some aspects of the present invention to provide a multi-dose dry powder inhaler device, and Particularly such a device that allows convenient tracking of dosage and patient compliance. 
     In preferred embodiments of the present invention, a dry powder For delivery to a patient by inhalation is contained in a package having an opening through which the powder flows when the patient inhales. The powder is deaggregated and mobilized by application of a magnetic field. Preferably, the field interacts with the package, engendering rapid motion thereof, which deaggregates the powder. 
     According to an other aspect of the present invention, an electrostatic valve screen is created by means of an alternating electrostatic field in a vicinity of the opening, so as to trap particles of the powder and prevent their escape from the package except during inhalation. 
     In some preferred embodiments of the present invention, the alternating electrostatic field is applied using electrodes at either side of the opening. Only when air is made to flow through the opening at a rate above a given threshold, which is generally determined by the voltage applied between the electrodes, can the powder flow out through the electrostatic valve screen. The voltage is preferably set so that the flow rate passes the threshold when the patient inhales, whereby the powder is drawn out of the package and into the patient&#39;s lungs. 
     In some preferred embodiments of the present invention, the package comprises flexible side walls, which are made to vibrate by application of the magnetic field. The vibration of the walls deaggregates the powder in the package and generates air flow which suspends the powder in the air inside the package. 
     In some of these preferred embodiments, the side walls of the package are coupled to electrical wiring, preferably to coils in the form of electrical conductors applied to a surface of the walls in the manner of a flexible printed circuit. One or more permanent magnets apply a fixed magnetic field to the package. The coils on the walls of the package are driven by an alternating electrical current, generating a field that interacts with the fixed magnetic field and thus causes the walls to vibrate. Preferably, the walls comprise an array of coils, which are driven cooperatively to control the mode of vibration of the walls and thus regulate the air flow inside the package. 
     Preferably, the external magnetic field has a component in a direction perpendicular to a coil axis, in the plane of the coils, causing the walls to vibrate along the axis. Alternatively or additionally, the magnetic field has a component perpendicular to the plane of the coils, causing lateral vibrations. 
     In other preferred embodiments, the side walls of the package comprise a magnetic material, which is preferably coated on a surface of the walls. The magnetic field is applied by driving an electromagnet outside the package with an alternating current, which thus causes the walls to vibrate. 
     Preferably, the flexible side walls are made to vibrate at a resonant vibration frequency thereof, in order to maximize the vibrational energy. Most preferably, a frequency of the alternating current applied to the coils on the walls or to the electromagnet is set so as to engender the resonant vibration. In a preferred embodiment, the frequency of the alternating current is swept through a range of frequencies, preferably including the resonant frequency, and is then set at the Frequency that maximizes the effectiveness of deaggregation, which is typically the frequency that maximizes the wall vibration. For this purpose, a vibration sensor is preferably coupled to the wall and provides feedback for use in controlling the frequency of the alternating current. In another preferred embodiment, the vibration sensor is coupled in a positive feedback loon to a driver that provides the alternating current, causing the loop to spontaneously oscillate at or near the resonant frequency. 
     In still other preferred embodiments of the present invention, the powder particles comprise an electrically-or magnetically-active component, preferably in the form of a coating on or a compound in the particles. In some of these preferred embodiments, in which the particles are magnetically active, the application of the magnetic field deaggregates the particles without the necessity of vibrating the walls of the package. Preferably, the field is driven to alternate at or near a resonant motion frequency of the particles. 
     In other preferred embodiments, the electrically-active component enables charging of the particles with a low work function, by contact of the particles with a conductive area or the walls. The charged particles then interact with the electrostatic screen with enhanced efficiency. 
     In some preferred embodiments of the present invention, a powder inhaler device, operating as described hereinabove, comprises a disposable package, which is introduced into and actuated by a reusable control and power unit. Preferably, the package is a part of a multi-dose cartridge, which most preferably comprises multiple packets of the dry powder, which are actuated in succession. In a preferred embodiment, the control and power unit includes a dose counter, as well as an appropriate user interface, which informs and reminds a patient as to dosage to be administered. The dose counter can also be used to record patient dosage and compliance data to be read out subsequently by medical caregivers. 
     There is therefore provided, in accordance with a preferred embodiment of the present invention, an inhaler device for administration of a dry powder to a patient, including: 
     a package containing a dose of the dry powder; and 
     a magnetic field generator, which produces a magnetic field in a vicinity of the package, causing motion of particles of the powder so as to deaggregate the powder in the package, whereby the powder is inhaled by the patient. 
     Preferably, the package includes walls made of a flexible material, which vibrate under the influence of the magnetic field so as to impart the motion to the particles. 
     Further Preferably, the package includes electrical wiring coupled to at least one of the walls and a control unit which drives a time-varying current through the wiring, causing the walls to vibrate due to interaction of the current with the magnetic field. Most preferably, the wiring includes a circuit trace printed on at least one of the walls, which forms a plurality of coils. In a preferred embodiment, the control unit drives the plurality of coils at respective relative phases so as to induce a desired mode or vibration of the at least one of the walls. 
     Alternatively, the walls include a magnetic material, and the field generator includes an electromagnet, which produces a time-varying magnetic field, causing the walls to vibrate due to interaction of the magnetic material with the magnetic field. Preferably, the magnetic material includes a coating on the one or more of the walls. 
     In a preferred embodiment, the walls made of the flexible material include opposing side walls of the package, which vibrate in a controlled mutual phase relationship. Preferably, the opposing side walls are driven to vibrate in phase or alternatively, in mutually opposite phases so as to pump the powder out of the package. 
     Preferably, the walls are driven to vibrate at a frequency approximately equal to a resonant vibration frequency thereof. In a preferred embodiment, the device includes a driver circuit, which provides an alternating current of adjustable frequency to drive the vibration of the walls, and a vibration transducer coupled to one of the walls, which transducer provides feedback to the driver circuit, so that the frequency of the alternating current is adjusted such that the walls vibrate at approximately the resonant vibration frequency. Preferably, the driver circuit and transducer are arranged in a self-oscillating positive feedback loop. 
     In another preferred embodiment, the device includes a vibration sensor, which generates signals responsive to vibration of the walls, and a control unit, which receives the signals from the vibration sensor and, responsive thereto, controls the inhaler device so as to regulate an energy of vibration of the walls. Preferably, the control unit provides an alternating current of adjustable frequency to drive the vibration of the walls, and adjusts the frequency of the alternating current in order the maximize the energy of vibration. 
     In a preferred embodiment, the powder includes magnetized particles, and the field generator produces a time-varying magnetic field which interacts with magnetic fields of the particles, causing the particles to move. Preferably, a frequency of the time-varying magnetic field is adjusted so that the particles oscillate at appximatelly a resonant frequency thereof. 
     In still another preferred embodiment, the package includes a multi-dose cartridge, such that multiple doses of the dry powder are administered to the patient in succession, and the device includes a dose counter which tracks the administration of the doses. 
     There is further provided, in accordance with a preferred embodiment of the present invention, an inhaler device for administration of a dry powder to a patient, including: 
     a package containing a dose of the dry powder and having an opening through which the powder exits the package and is inhaled by the patient; and 
     an electrostatic valve screen, which traps the powder inside the package by generating a time-varying electrostatic field across the opening. 
     Preferably, the valve screen includes a pair of electrodes positioned on opposing sides of the opening. 
     Further preferably, the electrostatic valve screen allows the powder to pass through the opening when a rate of air flow through the opening exceeds a predetermined threshold, wherein the threshold is chosen such that inhalation by the patient generates an air flow through the opening in excess of the threshold. 
     Preferably, the electrostatic field causes particles of the powder to oscillate in a vicinity of the opening. 
     There is also provided, in accordance with a preferred embodiment of the present invention, a method for deaggregation of a dry powder for administration to a patient, including applying a magnetic field so as to cause motion of particles of the powder, whereby the powder is inhaled by the patient. 
     Preferably, the powder is contained in a package having walls made of a flexible material, and applying the magnetic field includes magnetically inducing vibration of the walls so as to impart the motion to the particles. Further preferably, inducing the vibration includes driving a time-varying current in wiring coupled to at least one of the walls, which current interacts with the magnetic field to induce the vibration of the walls. In a preferred embodiment, driving the current includes driving current in different portions of the wiring at respective, relative phases so as to induce a desired mode of vibration of the walls. 
     Alternatively, inducing the vibration includes applying a time-varying magnetic field, which interacts with magnetic material in the walls to induce the vibration. 
     In a preferred embodiment, inducing the vibration includes controlling relative phases of vibration of different ones of the walls. 
     In a further preferred embodiment, inducing the vibration includes driving the vibration at approximately a resonant vibration frequency of the walls. Preferably, inducing the vibration includes sensing vibration of one of the walls and adjusting a frequency of the vibration responsive to the sensing. 
     In still another preferred embodiment, the method includes magnetizing the particles, wherein applying the magnetic field includes applying a time-varying magnetic field which interacts with magnetic fields of the particles, causing the particles to move. 
     There is additionally provided, in accordance with a preferred embodiment of the present invention, a method for administration of a dry powder to a patient, including: 
     providing the dry powder in a package having an opening through which the powder exits the package and is inhaled by the patient; and 
     generating a time-varying electrostatic field across the opening so as to trap the powder inside the package until the patient inhales. 
     Preferably, generating the field includes adjusting the strength of the field so as to allow the powder to pass through the opening only when a rate of air flow through the opening exceeds a predetermined threshold, wherein the threshold is chosen such that inhalation by the patient generates an air flow through the opening in excess of the threshold. 
     Further preferably, generating the electrostatic field causes particles of the powder to oscillate in a vicinity of the opening. 
    
    
     The present invention will be more fully understood from the following detailed description of the preferred embodiments thereof, taken together with the drawings in which: 
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic, partly cutaway, pictorial illustration of an inhaler device, in accordance with a preferred embodiment of the present invention; 
     FIG. 2 is a schematic, sectional illustration showing details of a powder package within the inhaler of FIG. 1, in accordance with a preferred embodiment of the present invention; 
     FIGS. 3A,  3 B and  4  are schematic illustrations showing operating modes of the package of FIG. 2, in accordance with preferred embodiments of the present invention; 
     FIG. 5 is a schematic illustration showing details of an inhaler device, in accordance with another preferred embodiment of the present invention; 
     FIG. 6A is a schematic, sectional illustration of a particle of a dry powder for delivery to a patient by inhalation, in accordance with a preferred embodiment of the present invention; 
     FIG. 6B is a schematic illustration showing details of an inhaler device for delivery of the powder of FIG. 6A, in accordance with a preferred embodiment of the present invention; 
     FIG. 7 is a schematic, pictorial illustration of a multi-dose powder dispenser cartridge, in accordance with a preferred embodiment of the present invention; 
     FIG. 8 is a block diagram that schematically illustrates dose counting circuitry used in an inhaler device, in accordance with a preferred embodiment of the present invention; 
     FIG. 9 is a flow chart that schematically illustrates a method for tracking dosage of a medication administered by inhalation, in accordance with a Preferred embodiment of the present invention; 
     FIG. 10 is a block diagram that schematically illustrates Frequency control circuitry used in driving an inhaler device, in accordance with a preferred embodiment of the present invention; 
     FIG. 11 is a block diagram that schematically illustrates frequency control circuitry used in driving an inhaler device, in accordance with another preferred embodiment of the present invention; and 
     FIG. 12 is a schematic, sectional illustration showing details of a powder package, in accordance with another preferred embodiment of the present invention. 
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     Reference is now made to FIGS. 1 and 2, which schematically illustrate an inhaler device  20 , in accordance with a preferred embodiment of the present invention. FIG. 1 is a schematic, partly cutaway, pictorial view, and FIG. 2 is a sectional detail view. 
     Device  20  comprises a powder package  22 , preferably in the form of a disposable, replaceable cartridge, which is inserted into a device housing  24 . Package  22  comprises an upper side wall  23  and a lower side wall  25 , which enclose a volume  26  in which a medication in the form of a dry powder  66  is contained. The side walls preferably comprise a flexible plastic material, such as Mylar, on which electrical conductors are printed, in the manner of a printed circuit, as is known in the art. The electrical conductors form one or more coils or current loops on each of the side walls. In the embodiment of FIGS. 1 and 2, an upper exterior coil  28 , an upper exterior intermediate coil  30 , an upper interior intermediate coil  32  and an upper interior coil  34  have the form of traces printed on wall  23 , and a lower exterior coil  58 , a lower exterior intermediate coil  60 , a lower interior intermediate coil  62  and a lower interior coil  64  have the form of traces printed on wall  25 . Different numbers of coils or loops, as well as coils and loops of different shapes and forms, may similarly be used. 
     An upper permanent magnet  36  and a lower permanent magnet  38 , or alternatively electromagnets or magnetic materials of other types, are placed adjacent to package  22  and produce a generally static magnetic field in and around the package. More preferably the poles of the magnets are configured to create a magnetic field component perpendicular to the axes of the coils, i.e., in the plane of the walls. In a preferred embodiment, the poles are configured as a North-North pair, with the coils in the gap between the poles. A control unit  40 , powered by a battery  42 , drives an alternating current through the coils, which interacts with the magnetic fields of magnets  36  and  38  so as to induce vibrations in walls  23  and  25 , as described further hereinbelow. Preferably, the frequency of the alternating current is adjusted so that the walls are driven to vibrate at a dominant resonant vibrational frequency of the walls, as ether described hereinbelow. of the alternating current is adjusted so that the walls are driven to vibrate at a dominant resonant vibrational frequency of the walls, as further described hereinbelow. 
     Optionally, device  20  uses an electrostatic valve screen  45  to prevent escape of particles of powder  66  through openings  41  and  43  except when the patient inhales. The screen takes advantage of the fact that the particles in volume  26  typically acquire an electrostatic charge by contact with the walls of package  22 . A high-voltage generator  52  is coupled via an upper contact  48  and a lower contact  50  to drive an upper electrode  44  and a lower electrode  46 , respectively, at opposite sides of opening  41 , and similarly via contacts  68  and  70  to drive electrodes  74  and  76 , respectively, at the sides of opening  43 . (Although only a single pair of electrodes is shown at the sides of each opening  41  and  43 , it will be understood that multiple electrodes may similarly be used for this purpose.) Preferably, the generator drives the electrodes to produce an alternating electrostatic field in openings  41  and  43  having a peak amplitude of about 3000 volts, at a frequency between 1 and 100 Hz. If the dimensions of package  22  and the characteristics of the field are appropriately chosen, the electrostatic valve screen and the coils on side walls  23  and  25  can be driven at the same frequency, using a common frequency generator in control unit  40 . 
     Optionally, device  20  uses an electrostatic valve screen to prevent escape of particles of powder  66  through openings  41  and  43  except when the patient inhales. The screen takes advantage of the fact that the particles in volume  26  typically acquire an electrostatic charge by contact with the walls of package  22 . A high-voltage generator  52  is coupled via contacts  48  and  50  to drive electrodes  44  and  46 , respectively, at opposite sides of opening  41 , and similarly via contacts  68  and  70  to drive electrodes  74  and  76 , respectively, at the sides of opening  43 . (Although only a single pair of electrodes is shown at the sides of each opening  41  and  43 , it will be understood that multiple electrodes may similarly be used for this purpose.) Preferably, the generator drives the electrodes to produce an alternating electrostatic field in openings  41  and  43  having a peak amplitude of about 3000 volts, at a frequency between 1 and 100 Hz. If the dimensions of package  22  and the characteristics of the field are appropriately chosen, the electrostatic valve screen and the coils on side walls  23  and  25  can be driven at the same frequency, using a common frequency generator in control unit  40 . 
     When the electrostatic field is on, charged particles in the vicinity of openings  41  and  43  oscillate and are trapped in the electrostatic field, as long as the air flow velocity through the openings is below a given threshold. The threshold level is a function of the field strength and frequency and may be adjusted by varying one or both of these parameters. Typically, the threshold air flow velocity is set to about 1 liter/min, and the actual flow rate exceeds this velocity only when the patient inhales. Thus, device  20  releases the powder from package  22  in synchronization with the patient&#39;s breath cycle, without the need for a flow sensor or active synchronization. 
     Alternatively, mechanical valves, as are known in the art, may be used to close off openings  41  and  43  during times other than the inhalation portion of the patient&#39;s breath cycle. 
     FIGS. 3A and 3B are schematic illustrations showing vibration of side walls  23  and  25  when control unit  40  drives the coils thereon, in accordance with preferred embodiments or the present invention. The solid lines show the side walls at one extremum of their vibration, and the dashed lines show the opposite extremum. The amplitude of the vibration (i.e., the distance between the extrema) is exaggerated for clarity of illustration. 
     In the embodiment of FIG. 3A, all of coils  28 ,  30 ,  32  and  34 , together with coils  58 ,  60 ,  62  and  64 , are driven in phase with one another. Therefore, walls  23  and  25  vibrate in phase with one another, thereby deaggregating and suspending powder  66 . Since the vibrations are in phase, the total volume containing the powder is largely constant despite the vibrations, so that there are only minimal pressure variations inside package  22 , and the powder is unlikely to be pumped out through one of the openings. 
     In the embodiment of FIG. 3B, however, the coils on wall  23  are driven in opposite phase to the coils on wall  25 . The vibrations of walls  23  and  25  are similarly oppositely phased, thus creating a pumping action that can be used to aid in expelling powder  66  when desired. 
     FIG. 4A is a schematic illustration showing another mode of vibration of side walls  23  and  25 , in accordance with a preferred embodiment of the present invention. In this case, coils  28 ,  30 ,  58  and  60  are driven in opposite phase to coils  32 ,  34 ,  62  and  64 , thus inducing a higher-order vibrational mode of the walls. Other vibrational modes can similarly be induced by appropriately varying the phases and, optionally, amplitudes of the currents used to drive the various coils. 
     FIG. 5 is a schematic illustration showing details of an inhalation device  80 , in accordance with another preferred embodiment of the present invention. Device  80  is largely similar to device  20 , described hereinabove, except that it uses a different technique to induce vibration of walls  23  and  25 . A package  82  is similar in construction to package  22 , except that this package has a magnetic coating  84  on the walls. The coating preferably comprises iron (Fe) or a ferrous compound, for example iron cobalt or gamma Fe2O3, which are widely used in the magnetic recording field. An upper electromagnet  86  and a lower electromagnet  88 , respectively comprising an upper coil  90  and a lower coil  92 , are placed at either side of package  82 . A driver  94  provides an alternating current to the coils, which thus generate a time-varying magnetic field. The field interacts with coating  84  on the side walls, inducing vibration of the walls. There may be multiple adjacent coils on each of electromagnets  86  and  88 , like the multiple coils on walls  23  and  25  of package  22 . Driver  94  may further control the phase of the currents supplied to the coils so as to vary the spatial distribution of the magnet field and thus affect the vibrational mode of the walls, as described hereinabove. 
     FIG. 6A is a schematic, sectional illustration of a particle of powder  96 , in accordance with still another preferred embodiment of the present invention. The particle preferably comprises a magnetic or electrically-active coating  99  applied around a core  98  containing a medication to be administered to a patient. Alternatively, the particle may comprise a magnetic core, to which the medication is applied as a coating. If the coating is of the electrically-active type, it preferably comprises a substance such as sodium, potassium or calcium, which acquires electrical charge with a low work function by contact with a conductive area of the walls of package  22  or with a suitable electrode in the package. The powder can then be more effectively trapped by the electrostatic valve screen, typically at a lower voltage than would otherwise be required. 
     FIG. 6B 1 s a schematic illustration showing details of an inhalation device  100  for use with particles of powder  96  having a magnetic coating  99 , in accordance with a preferred embodiment of the present invention. Device  100  and a powder package  102  therein are substantially similar in design and operation to device  80  and package  82  shown in FIG. 5, except that package  102  does not require magnetic coating  84  on its side walls. Instead, coating  99  of the particles of powder  96  interacts with the time-varying magnetic field generated by coils  90  and  92 , causing deaggregation and suspension of the particles in volume  26 . There is no need for vibration of side walls  23  and  25  for this purpose, as there is in the other embodiments described hereinabove. 
     FIG. 7 is a schematic, pictorial illustration showing a multi-dose powder dispenser cartridge  120 , in accordance with a preferred embodiment of the present invention. Cartridge  120  comprises a row of conjoined packets  122  containing a medication in dry powder form, to be dispensed by inhalation using a suitable device having the general form and function of device  20 , shown in FIG.  1 . Each of packets  122  takes the place of package  22  in device  20 , and functions in a generally similar manner. The packets are inserted in succession, as needed, into the inhaler device, preferably without separating the packets in the row one from another. Preferably, cartridge  120  is disposable, and is thrown away after the doses in all of packets  122  have been exhausted, whereas the inhalation device with control and power electronics is reused indefinitely. 
     When a dose of the medication is to be administered, one of packets  122  is slid into an operating position inside the inhaler device. A first protective strip  134  and a second protective strip  136  are peeled away, uncovering a first air opening  141  and a second air opening  143 . An alternating electrical current is driven through coils  128  and  158  on upper and lower walls  123  and  125 , respectively, of the packet, via coil contacts  124 . (For simplicity of illustration, the contacts for coils  158  are not shown in the figure.) As described hereinabove, the alternating current causes walls  123  and  125  to vibrate, thereby deaggregating the powder. 
     Preferably, a transducer  130  serves as a vibration sensor, generating signals responsive to the vibration of wall  123 , which signals are received via sensor contacts  132  by a controller of the inhalation device, such as control unit  40  of device  20 . The transducer signals are used in controlling the alternating current applied to the coils, most preferably to adjust the frequency of the current so as to maximize the energy of wall vibration, as described further hereinbelow. Preferably, transducer  130  comprises a pickup coil, in which a current flows responsive to movement of the coil in the external magnetic field applied to packet  122 , for example, by magnets  36  and  38 . Alternatively, transducer  130  may comprise an accelerometer or a microphone, which senses acoustic radiation produced by vibration of the walls of the packet (in which case the transducer may also be positioned adjacent to, rather than on, wall  123 ). 
     Cartridge  120  is advantageous in that it allows multiple doses to be dispensed in succession, conveniently and reliably. Other cartridge shapes and configurations may similarly be used for this purpose. For example, packets  122  may be arranged in a ring. 
     FIGS. 8 and 9 schematically illustrate circuitry and methods used in automatically tracking dosage administered by an inhaler device, in accordance with a preferred embodiment of the present invention. FIG. 8 is a block diagram of circuitry used for this purpose, and FIG. 9 is a flow chart illustrating the tracking method. The circuitry and method are preferably, although not necessarily, used in conjunction with a multi-dose cartridge, such as cartridge  120  shown in FIG.  7 . 
     Before the powder dose in one of packets  122  is released, a cell presence detector  160  detects that the packet is properly positioned in a dispensing position in the inhaler device. Detector  160  preferably detects an electrical resistance between contacts  124  or  132  on the packet and, assuming the resistance to be within a predetermined range, notifies control unit  40  of the presence or :he packet. Alternatively, detector  160  may detect a short circuit between suitable, dedicated terminals on the packet (not shown in the figures). Further alternatively, detector  160  may sense the position of packet  122  mechanically or optically, using sensing ,methods known in the art. 
     Once control unit  40  determines that the packet is suitably positioned, it enables the inhaler device to operate. The device is then actuated by means of operational keys l 4  and/or by a flow sensor (not shown), so as to apply electrical current to coils  128  and  158 . Preferably, electrostatic valve screens are applied at openings  141  and  143 , as described hereinabove, to keep the powder in the packet until it is inhaled by the patient. Bellowing actuation, a dose counter  162 , typically comprising a memory segment associated with control unit  40 , is incremented to record that the medication was administered. Preferably, the time and date of the dose, as provided by a real-time clock  168 , are also recorded in the memory. The patient or medical caregiver can then see on a display  166  a record of doses administered, for purposes of avoiding overdosage or underdosage and or tracking patient compliance. After the dose counter has been incremented, control unit  40  waits for detector  160  co indicate that a new packet  122  has been moved into position before allowing the device to be actuated again. 
     FIG. 10 is a block diagram that schematically illustrates circuitry used in controlling the frequency of the electrical current applied to coils  128  and  158 , in accordance with a preferred embodiment of the present invention. The purpose of controlling the frequency is typically to minimize the vibrational energy of walls  123  and  125  for a given input power to the coils. Such maximal energy is generally achieved when the frequency is such that the walls vibrate at a mechanical resonant frequency thereof. The resonant frequency may vary from packet to packet or from cartridge to cartridge as a result of differences in the dimensions and materials of the packets. For this reason, the circuitry of FIG. 10 is useful in adjusting the frequency for each packet. It will be understood that such circuitry may be applied, as well, to drive the coils of packet  22 , shown in FIGS. 1 and 2. 
     Control unit  40  receives signals from transducer  130 , indicative of the amplitude and frequency of vibration of the wall of packet  122 . The signals are processed to determine the energy of vibration of the wall, which is generally maximal when the wall is driven to vibrate at its mechanical resonant frequency, as noted above. The control unit varies the frequency of an oscillator  170  (which may also be implemented in software running on the control unit itself), which frequency is supplied to a driver amplifier  172 , coupled to coil  128 . As the frequency is swept through the resonant frequency of the wall, the control unit detects a corresponding peak in the vibrational energy sensed by sensor  130  and locks onto the peak frequency. 
     FIG. 11 is a block diagram that schematically illustrates a circuit for use in controlling the frequency of the current applied to coils  128  and  158 , in accordance with another preferred embodiment of the present invention. In this case, transducer  130  and driver amplifier  172  are included in a positive feedback loop, coupled by a phase compensation network, as is known in the art. The loop tends to oscillate at a resonant frequency that is determined by the resonant vibration frequency of wall  123 , since at this frequency the output signal of transducer  130  is typically maximized. Thus, maximal vibration of the walls of packet  122  (or, similarly, of packet  22 ) is achieved without the need for active frequency control by control unit  40 . 
     FIG. 12 is a schematic, sectional illustration of a powder package  180 , in accordance with another preferred embodiment of the present invention. The package has the form of a blister pack, for ease of manufacture, formed from an upper layer  182  and a lower layer  184  of a suitable plastic material. A blister  186  between the upper and lower layers, having at least one air flow opening  41 , holds powder  66 . A printed circuit coil  190  is formed on an outer surface of package  180  at one end thereof, which end is positioned between magnets  36  and  38 . The other end of the package is held in a holding clip  188 . When current flows in coil  190 , it causes vibration of the entire package  180 , rather than just the walls of blister  186 , but the deaggregation effect is substantially similar to that described hereinabove with respect to other preferred embodiments. 
     It will be appreciated that the preferred embodiments described above are cited by way of example, and the principles of the present invention may similarly be embodied in different configurations and combinations of the elements and concepts shown and described herein. The full scope of the invention is thus limited only by the claims.