Inhaler nozzle maintenance apparatus and method

A medication dispenser includes a thermal drop generator ejector head. Medication is maintained in a pressurized container connected to a valve under the control of control electronics and to a compliant chamber. Fluid flows from the container to the chamber and to the ejector head. In a first mode the dispenser is operable to dispense aerosolized medication. In a second mode the ejector head is purged with fluid from the container to maintain the ejector head.

TECHNICAL FIELD

This invention relates to apparatus and methods for maintenance of ejector nozzles such as thermal drop generators used in devices such as inhalers.

BACKGROUND OF THE INVENTION

Medications are often delivered to patients in the form of inhaled aerosols—gaseous suspensions of very fine liquid or solid particles in which medications are entrained. So-called pulmonary delivery of medication is in many instances a very efficient manner of delivering biological and chemical substances to the patient's bloodstream. Pulmonary delivery is especially efficient when the medication is delivered with a digitally controlled device such as a “metered dose inhaler” (“MDI”) or other type of inhaler that incorporates ejector heads that are suitable for creating aerosols having very small droplet size. Such inhalers are often used to deliver asthma medications directly into a patient's lungs where the medications are rapidly absorbed into the blood stream.

As with any device intended to deliver medication to a patient, it is essential that an inhaler is maintained in proper operating condition to ensure, among other things, that the proper dosage of medication is administered to the patient, and that the device is suitably clean. However, the ejector heads that are used in digital inhalers such as MDIs can become clogged over time and repeated use. Moreover, some types of medications can accumulate on the surfaces of the ejector head. In both cases, whether one or more nozzles becomes clogged or the nozzle orifice size is reduced due to accumulated residue, the dosage of medication delivered to the patient may be affected, resulting in a lower dosage than might be needed. Clogging and accumulated residue may also impact the cleanliness of the inhaler.

There is an ongoing need to provide inhalers with smaller and very precisely controlled drop sizes. As these requirements increase, there is an ongoing need to provide such inhalers and other medication delivery apparatus having improved reliability.

DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS

The device of the present invention is an inhalation system including an ejector head and fluid supply system coupled to a controller. The ejector head includes a plurality of individual nozzles that each ejects droplets of aerosol under the influence of the controller. The fluid supply system provides fluid to the ejector head nozzles at a pressure level that is modulated by the controller. The controller is configured to control both the operation of the ejector head nozzle ejection and the delivery of fluid to the ejector head nozzles via the fluid supply system.

The controller operates the fluid supply system to define two modes—an operating mode and a non-operating mode. During the operating mode the controller operates the ejector head to eject fluid droplets and the fluid supply system to supply fluid to the ejector head nozzles at an operating fluid supply pressure. During the non-operating or a nozzle maintenance mode the controller supplies fluid to the ejector head nozzles at a nozzle purge fluid supply pressure to allow fluid to purge air and/or blockages from the nozzles. In a preferred embodiment, the nozzle purge fluid pressure is greater than the operating fluid supply pressure.

The nozzle maintenance mode can be operable in response to a determination that the nozzles are not operating properly or it can be operable periodically. In an exemplary embodiment, the ejector includes a sensor such as a temperature sensor that is operable to determine that the nozzles are not operating properly. Upon a certain event, the sensor provides information to the controller indicative of an improper operation or a fault that triggers the controller to initiate the nozzle maintenance mode.

In an alternative embodiment, the inhalation system includes an information storage device or clock that accumulates information indicative of a time and/or number of drop ejections since a nozzle maintenance mode event. The nozzle maintenance mode may be initiated based on the accumulated time and/or number of drop ejections or usage of the inhaler since the previous nozzle maintenance mode. Of course, in yet another and perhaps most advantageous embodiment, the maintenance mode is activated or initiated based on an event or time/usage depending on what occurs first.

In an exemplary embodiment, the fluid supply system includes a reservoir system coupled to the ejector via a valve system. The controller modulates the fluid pressure at or being received by the ejector nozzles by opening and closing one or more valves of the valve system. The reservoir system includes a medicated fluid reservoir containing a supply of medicated fluid for ejection by the ejector nozzles during the operating mode. The valve system includes a valve operable by the controller that opens and closes during the operating mode to provide a stable operating fluid supply pressure by opening and closing a valve coupling between the medicated fluid reservoir and the ejector nozzles. In an exemplary embodiment, the ejector nozzles are thermal drop generator-type nozzles and the operating fluid supply pressure is a negative gauge pressure.

For background purposes, an exemplary embodiment of the drop generator ejector head comprising a thermal jet is a generally planar member having plural nozzles, each nozzle having an outlet orifice and a fluid chamber communicating with the fluid supply. The fluid chamber is a small reservoir for holding fluid prior to ejection of the fluid from the chamber through the orifice. The mechanism for ejecting the liquid from the chamber is a heat transducer proximate the fluid chamber that heats the fluid in the chamber to generate a vapor bubble in the fluid-filled chamber. Expansion of the vapor bubble in the chamber causes aerosolization of the fluid as it is ejected through the orifice. Other similar types of thermal drop generators would also suffice.

The reservoir system includes a purge reservoir containing purge fluid at a positive gauge pressure and a purge valve under control of the controller and coupling the purge reservoir to the nozzles. When a certain event or time occurs, a nozzle maintenance mode is initiated. The controller opens the purge valve coupling the positively pressurized purge reservoir to the nozzles such that purge fluid flow from the purge reservoir and out the nozzles.

In a first embodiment, the same medicated fluid reservoir and the purge reservoir are the same reservoir. In the first embodiment, the medicated fluid is utilized as purge fluid. In a second embodiment, the reservoir system includes separate reservoirs containing medicated fluid and purge fluid. In the second embodiment, there is a purge valve that is separate from the valve used for delivering medicated fluid.

FIG. 1is a flow chart showing the basic operational modes according to the present invention. With reference to that figure, a pharmaceutical container6, shown schematically as a block surrounding the flow chart, incorporates nozzle maintenance apparatus and methods. The nozzle maintenance apparatus according to the illustrated invention is operational in two primary modes. The first mode, or the “operational mode” is represented by block8. The second mode, or “non-operational mode” is represented by block10, and is also referred to herein as the nozzle maintenance mode10.

As described in detail below, and as illustrated inFIGS. 2 and 3, pharmaceutical container6is exemplified in one example by a metered dose inhaler (MDI) that is operable two basic functional modalities defined above as operational mode8and maintenance mode10. Operational mode8is the mode typically used when MDI6is being used to deliver medication to a patient—it is the normal operating mode for the inhaler. In this mode, the pressure in both the ejector head20and compliant chamber16, which as detailed below serves as a small reservoir for the supply of medication that is to be delivered through the ejector head, is maintained at a lower pressure value (referred to herein as “negative”) relative to the gauge pressure that is maintained in the supply of medication in fluid reservoir14. The relative negative pressure in the ejector head and compliant chamber in operational mode8ensures stable operation of the ejector head20, and prevents, for example, drooling of medication through the nozzles. A supply of medication is contained in reservoir14, which may be any appropriate type of pressurizable fluid container such as a spring-loaded bag design or other type of container. The medication in reservoir14is typically in solution form. Fluid in reservoir14is maintained at an elevated pressure relative to the pressure of compliant chamber16.

Compliant chamber16normally contains a desired amount of medication ready to be ejected through the ejector head20. Medication from reservoir14is resupplied to compliant chamber16when the amount of medication in the chamber falls below a predetermined amount. When medication is to be delivered to the patient, for example when the user depresses a switch30on the MDI, a control system energizes resistors associated with plural nozzles (not shown) in ejector head20, causing the resistors to heat and thereby aerosolize the medication solution. The patient inhales the droplets thus expelled.

The gauge pressure of the compliant chamber16is monitored and regulated closely by the control electronics. When the pressure falls outside of a predetermined normal range of operation, as for example when the supply of medication in the compliant chamber is nearly exhausted, the control electronics open the electromechanical valve to allow fluid to flow from the reservoir14into the compliant chamber16. Fluid flows from the higher pressure reservoir14into the lower pressure compliant chamber16until the pressure in the chamber is within the normal range for operation, at which time the control system closes valve17.

The second primary operational mode is maintenance mode10. In maintenance mode10, the control system26operates in response to a signal from an electronic control system to pressurize the compliant chamber and the ejector head20such that the pressure in these structures is positive relative to the pressure immediately outside of the ejector head. As detailed below, this reversal in pressure from the relatively lower (negative) pressure in the ejector head and compliant chamber in operational mode8to the relatively higher (positive) pressure in the maintenance mode10is preferably accomplished by pressurizing the entire fluid delivery system by opening valve17and disabling resistor firing. The positive pressurization state of the fluid delivery system in the maintenance mode10purges the nozzles of any fluid remaining thereon, and has the effect of pushing air through the nozzle, thereby cleaning them, eliminating clogs and restoring the nozzles to normal operations. Once the maintenance mode10is complete (as detected by tests run by control system26, described below), the MDI6returns to operational mode8.

With specific reference now toFIGS. 2 and 3, the illustrated embodiment of the inventive apparatus and methods are described herein as they are embodied in pharmaceutical container6, which in this case is a pulmonary delivery mechanism known as a metered dose inhaler (MDI) and is at times referred to herein as MDI6. MDIs such as the MDI6described herein are widely used for the delivery of aerosolized medications such as asthma medication and there are many variations of MDI delivery systems on the market. An MDI typically combines a drug with a propellant in a container that may be pressurized. The drug may be in the form of a liquid or a fine powder. Actuation of the device releases metered doses of aerosolized drug that is inhaled by the patient. The drop generator ejector head described herein may be of the type described in U.S. patent application Ser. Nos. 09/761,287 (Publication No. U.S. 2002/0092519 A1) and 10/000,425 (Publication No. 2003/0081072 A1).

It will be appreciated that the MDI6illustrated inFIG. 2is intended only to illustrate one of many possible pharmaceutical containers and delivery systems that may incorporate the inventions described herein. As examples, the invention may be used with any ejection system such as piezo and other nozzle-based multiple use ejectors, and other thermal ejectors. As used herein, the term “medication” is used generally to refer to any fluid or compound, whether biological, chemical or other, delivered to a patient, whether for treatment of a medical condition or some other purpose. Other common words may be used interchangeably, such as “pharmaceutical” or “bioactive agent” and similar words.

Before turning to a detailed description of the nozzle purging apparatus and methods of the present invention, the primary components of container6will be described with specific reference toFIGS. 2 and 3.

Container6comprises an inhaler housing12that is configured to contain a reservoir14of medication, which as noted is typically provided in solution form. The medication reservoir14is coupled through a medication-carrying conduit15to a compliant chamber16. An electromechanical valve17is interposed in conduit15between medication reservoir14and compliant chamber16. Valve17is under the control of the control electronics, described below. Compliant chamber16is fluidly coupled, as for example by a needle and septum interconnection or other airflow regulator such as a thermal resistive element or piezo element, to a conduit18in the housing so that the medication in reservoir14is directed to a drop generator head, illustrated schematically at20(referred to as “ejector head20”), that carries multiple drop generators comprising nozzles that are configured for generating appropriately sized aerosolized drops or particles. The drop generator head used in an MDI such as the one illustrated typically include resistor-based nozzles that eject droplets of fluid for inhalation such as those described above. It will be appreciated that the illustration ofFIG. 2is schematic, and that an MDI must necessarily be designed to have the capability for the patient to inhale a substantial volume of air in which the aerosol is entrained.

Pressure sensors34and36are provided to detect and monitor the pressure of both the ejector head20and the compliant chamber16, respectively, both of which are under the control of control system26and which are interconnected with the control system with an appropriate flex circuit33. Pressure sensors34and36may be of any appropriate type of sensor and may be positioned either externally to ejector head20and compliant chamber16, or internally, as desired. Moreover, depending upon the structural design used in making MDI6, a single pressure sensing unit may be configured for reading the pressure of both compliant chamber16and ejector head20.

The combined components of the fluid delivery system utilized in MDI6are identified herein and in the drawings with reference number38(see, e.g.,FIG. 4). Fluid delivery system38includes medication reservoir14, compliant chamber16, conduits15and18and electromechanical valve17and ejector head20.

The drop generator or ejector head20is electrically interconnected to a controller, shown schematically at24, which is part of the MDI electronics control system26, for example with a flex circuit22. Among other functions described below, controller24generates and sends suitably conditioned control signals to drop generator head20to initiate delivery of the medication to the patient by firing the nozzles contained in the ejector head. The MDI control system26includes controller24, a power supply28and operator switch30. The controller24includes control circuitry that responds to the switch signal by directing to the drop generator head controlled current pulses for firing the drop generators as required. It will be appreciated that the control system can be configured in any of a number of ways and, most preferably, integrated with the housing14of the inhaler. Controller24includes appropriate processors and memory components. It will be appreciated that in some circumstances the circuitry that defines controller24may be incorporated into a real time clock circuit, and vice versa. Controller24also monitors the temperature of drop generator head20and specific nozzle areas within the ejector head. With respect toFIG. 2, the pressure sensor34may also be used to represent a temperature sensor35. Suitable temperature sensors35include integrated circuit temperature sensors such as thermistors and resistors, thin film metals, metal oxide semiconductor temperature sensors, CMOS or MOS transistors, bipolar transistors, circuits defining a Wheatstone bridge, and others. Depending upon the specific usage, more than one temperature sensor may be utilized. Although not shown, MDI6may include a display on housing12such as a liquid crystal display to alert the user to the status of the unit.

In the case where MDI6is configured for delivery of medication via inhalation by the patient, the drop generator or ejector head20is typically located near a mouthpiece32. The ejector head20illustrated inFIG. 2is thus located inwardly of the mouthpiece32to allow the aerosolized medication to mix with airflow as the patient inhales. It will be appreciated that the control system26and the arrangement and orientation of the drop generator head20in housing12provide for both precise metering of the amount of droplets ejected and of the amount of medication expelled, as well as the generation of suitably small droplets. That is, the expulsion of the medication from the medication reservoir14need not be accompanied with other mechanisms for reducing the volume of ejected liquid to suitably small droplets. The ejection route of medication aerosolized out of mouthpiece32is shown schematically with a series of arrows A inFIG. 2.

Various control mechanisms are used with metered dose inhalers, depending upon the nature and level of control that the prescribing physician wishes to provide to the patient. When such controls are included (none are shown in the illustrated embodiment) they may be activated or inactivated to suit the particular circumstances.

Control system26may also include a programming interface44connected to controller24and externally exposed at the rearward end of housing12(FIG. 2) for connection to a computer. Programming interface44includes conductor pads46(FIG. 3) that interconnect the interface through traces (as in a flex circuit) and buss interfaces to controller24. The illustrated embodiment of programming interface44may be replaced, for example, with any suitable programming interface, including an infrared compliant data link, or other similar programming interface.

The details of operation of MDI6will now be explained with reference to the flow chart ofFIG. 5. The operational mode8is depicted at the top of the flow chart and as detailed above is the mode during which medication may be delivered to the patient. In this mode, the pressure of the compliant chamber16and the ejector head20is as described above at a negative gauge pressure relative to the gauge pressure that is maintained in the medication reservoir14. At all times when MDI6is powered, control system26monitors various operational aspects of the MDI to determine whether the unit is operating properly and to thereby determine if a maintenance mode is necessary. If according to this ongoing monitoring the control system determines that MDI6is operating within predetermined normal values for any given operational aspect that is being monitored, then the system remains in operational mode8. If a monitored operational aspect indicates that the system is operating outside of a predetermined normal value or has exceed a predetermined critical value, then the control system26initiates a maintenance mode10.

There are several operational aspects that system26may monitor to determine whether MDI6is operating normally, or abnormally as when a critical value has been reached, and thus whether a maintenance mode10should be initiated. As one exemplary embodiment of an operational aspect that may be monitored, the temperature of the resistors in ejector head20(step50) may be monitored. If the temperature of the ejector head20(or monitored portions of it) is within a predetermined normal operation range (step52), then control system26deems the unit to be operating properly and MDI6remains in the operational mode8.

When the nozzles in ejector head20become clogged or if, for example, residues from medication dispensed through the ejector accumulate on the nozzles, or bubbles retained in the nozzles prevent the nozzles from operating properly, the temperature of the ejector head20rises. As noted above, the primary reason for an increase in temperature of ejector head20is the failure of liquid to escape the nozzles and hence carry heat away from the nozzles in the ejected fluid. If control system26senses that the temperature of the ejector head20(or portions of it) has risen above the predetermined normal operation range (step52) and/or has reached a predetermined critical value, then control system26initiates maintenance mode10.

As an alternative embodiment, control system26includes an information storage device or clock that accumulates information indicative of a time and/or number of drop ejections since a nozzle maintenance mode10last occurred. A maintenance mode10may be initiated based on the accumulated time and/or number of drop ejections or usage of the inhaler since the previous maintenance mode. For example, a predetermined critical value stored in control system26may be a number of nozzle firings (i.e., the number of times that the ejector head has been activated) since the last maintenance mode. If the number of nozzle firings exceeds the predetermined critical value, then a maintenance mode10is initiated. As still another example, an accumulated time since the last maintenance mode may be monitored as an operational aspect. Thus, a maintenance mode10may be initiated based on the time that has lapsed between the current time and the last previous maintenance mode.

Regardless of the particular type of operational aspect that controller26is monitoring, when a critical value has been detected by controller26a maintenance mode10is initiated and switch30is disabled so the patient cannot dispense medication. Control system26then opens valve17for a period of time sufficient to allow fluid to be flushed through the nozzles. As the fluid enters the compliant chamber16and ejector head20from the relatively higher pressure reservoir14, the gauge pressure in the compliant chamber16and ejector head20rises and becomes positive. As fluid moves through the compliant chamber and the ejector head, air is pushed out ahead of the fluid and the combination of air moving through the nozzles and fluid flowing through them tends to clear any clogged nozzles or nozzles that have residue accumulated on them. The resistors in ejector head20are not fired during this positive purging mode.

Control system26then closes valve17and the compliant chamber16and ejector head20return to the normal pressure state—negative relative to the positive pressurized state of reservoir14. At this time, control system26may optionally initiate a round of test firings (step54) of the ejector head20, while monitoring nozzle temperature, to determine if another positive pressure purge according to maintenance mode10is necessary. If after the test firings at step54the temperature of the ejector head is within the predetermined normal range, then no further purging is needed and then switch30is enabled. If the temperature after the test firings is outside of the predetermined normal range, further purging is necessary and another maintenance mode10is initiated. If this maintenance cycle is successful in restoring the ejector head to an operational condition (as determined by ejector head temperature), then switch30is reactivated. If repeated maintenance cycles fail to resolve the problem, the switch30remains disabled and the unit may require servicing since the proper dosage of medication may not be delivered if some nozzles are clogged.

Turning now toFIG. 6, an MDI6may be configured to use more than one supply reservoir14. In the embodiment illustrated inFIG. 6compliant chamber16and ejector head20are supplied fluid from two reservoir chambers, each of which is fluidly connected to the compliant chamber16with an independently controlled electromechanical valve. Thus, medication reservoir14is the same type of supply reservoir as described above with respect to the embodiment ofFIGS. 2,3and4. However, MDI6shown inFIG. 6includes a second pressurized fluid reservoir identified as supply60. In the embodiment illustrated, supply60is a supply of maintenance fluid. The maintenance fluid may include compounds intended to sterilize ejector head20during maintenance mode10operations. The maintenance fluid may include any number of appropriate cleaning compounds, including for example ethanol or sterilized water, etc.

Operation of the MDI shown inFIG. 6is similar to the bimodal operation described above with respect to the single-pressurized reservoir14shown inFIG. 2. During operational mode8, compliant chamber16and ejector head20are maintained at a relatively lower pressure than medication reservoir14. Valve17, which is under the control of the control electronics in control system26periodically opens valve17when in operational mode8to resupply medication to compliant chamber16. When it is necessary to perform a pressurized maintenance mode10, valve17is kept closed, the switch30(not shown inFIG. 6) is disabled, and valve62which is plumbed into conduit64exiting supply60is opened, thereby initiating positive pressurization of the compliant chamber16and ejector head20. This positively pressurized flushing is identical to the maintenance mode10described above.

When control system26has determined that ejector head20is once again operational (by the temperature of ejector head20during test firings, as described above), valve62is closed so that the MDI6returns to operational mode8. A supply of medication from medication reservoir14may then be provided to compliant chamber16by operation of valve17, if needed.

An MDI6incorporating the nozzle maintenance system described herein may be used with more than two pressurized supply reservoirs as described with reference toFIG. 6. For example, in some cases an MDI will utilize two separate medication supply reservoirs—each filled with a different type of medication—and a separate maintenance supply reservoir. Each reservoir includes a valve that is independently controlled by the control electronics.

It will be appreciated that the volume of the compliant chamber16is preferably small—preferably less than 1 cm3. The relatively low volume of compliant chamber16enables switching between operational mode8and maintenance mode10without flushing an undue amount of fluid (whether from a medication from reservoir14or a maintenance fluid supply60) out of the system.

It will further be appreciated that those of ordinary skill in the art will recognize that modifications may be made to the systems and structures described herein without departing from the scope of the invention. For example, in the embodiments described above, fluid is maintained in a pressurized state in a supply reservoir and is supplied to the ejector head through and electronically activated valve. In one alternative embodiment, the supply reservoir could be maintained in a negative pressure state relative to the pressure in the compliant chamber, for example with a negative gauge pressure spring bag design used for the supply reservoir. When positive pressure is required to purge the ejector head, a mechanically operated mechanism may be used to engage the spring bag and to thereby force fluid into the fluid delivery system under positive pressure.

Finally, while the fluid supply reservoirs used in an MDI6are preferably replaceable, for instance, with a needle and septum type connection with the fluid conduits leading to the electromechanical valves, the MDI6may be fabricated as a disposable unit.

Having here described illustrated embodiments of the invention, it is anticipated that other modifications may be made thereto within the scope of the invention by those of ordinary skill in the art. It will thus be appreciated and understood that the spirit and scope of the invention is not limited to those embodiments, but extend to the various modifications and equivalents as defined in the appended claims.