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

• US 6,971,383 B2
• Filed: 01/24/2001
• Issued: 12/06/2005
• Est. Priority Date: 01/24/2001
• Status: Expired due to Term

• Current Assignee: Oriel Therapeutics, Inc. (Novartis Ag)
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Crowder, Timothy M., Hickey, Anthony J.
• Primary Examiner(s): PATEL, MITAL B
• Application Number:
  US10/204,609
• Publication Number:
  US 20040123864A1
• Time in Patent Office: 1,777 Days
• Field of Search: 128/203.15, 128/203.12, 128/203.21, 128/200.16, 128/200.14, 239/102.1, 239/102.2, 604/58
• US Class Current: 128/203.15
• CPC Class Codes: A61M 15/0048 the dosages being arranged in a plane, e.g. on diskettes
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/50 with microprocessors or computers

Abstract

Dry powder inhalers (FIG. 1) 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 being administered. The multi-dose dry drug package (FIG. 2) a piezoelectric polymer substrate which flexes to deform and provide mechanical oscillation in a selected region of the package corresponding to the dry powder drug which is dispersed during inhalation by a user. Control system (FIG. 12) employs fuzzy logic to relate in response to a user'"'"'s inspiratory effort.

Claims

1. A method of controlling the active delivery of a dry powder drug in an inhaler configured with an active energy assisted drug dispersion system, comprising the steps of:

establishing a priori a flowability characterization of a plurality of dry powder drug formulations;

measuring the airflow rate of a user using the dry powder inhaler;

determining a degree of membership of the flowability of the drug to be dispersed utilizing a first fuzzy logic function;

determining a degree of membership of the measured airflow rate of the user with a second fuzzy logic function; and

controlling an excitation signal directed to the active energy system of the inhaler based on the determined degrees of membership.

2. A method according to claim 1, wherein the steps of controlling comprises determining a degree of membership with a third fuzzy logic function, the degree of membership associated with the values associated with the determined degrees of membership to the first and second fuzzy logic functions.

3. A method according to claim 1, wherein the first fuzzy logic function associated with the flowability of the drug analyzes the propensity for the drug to be cohesive, and wherein the second fuzzy logic function associated with the measured inspiratory airflow rate of a user using the dry powder inhaler determines the degree of membership based on a dynamically measured airflow rate of a user.

4. A dry powder inhaler having an active energy assisted dispersing system, comprising:

a housing configured to receive a multi-dose dry powder package therein, said housing having an airstream exit flow path;

a control system positioned in said housing, said control system comprising;

a controller;

a power source operably associated with said controller;

a transformer operably associated with said controller and said power source configured to generate excitation energy directed to a selected region of the multi-dose dry powder package; and

computer readable program code programmed in said controller to determine the excitation energy directed to the multi-dose dry powder package.

5. A dry powder inhaler having an active energy assisted dispersing system according to claim 4, further comprising an air flow sensor positioned in said exit flow path, said air flow sensor operably associated with said controller, and wherein said computer readable program code further comprises computer code which considers the measured airflow rate to determine the excitation energy directed the dry powder package.

6. A dry powder inhaler having an active energy assisted dispersing system according to claim 5, further comprising computer readable computer program code which establishes a fuzzy logic model of the flowability of the dry powder formulation being administered and an associated suitable excitation energy, and wherein said computer readable computer program code which determines the excitation energy considers the results of the fuzzy logic flowability model to determine the excitation energy directed the dry powder package.

7. A dry powder inhaler having an active energy assisted dispersing system according to claim 4, further comprising a disposable multi-dose dry powder package having a plurality of spatially separated dry powder drug doses held thereon, said package including a piezoelectric polymer film substrate and a plurality of spatially separate electrical signal paths thereon, said dry powder package positioned in said housing such that said excitation signal is directed to a selected one of said plurality of signal paths to thereby deliver an excitation signal to cause the package to oscillate in the vicinity of the drug dose held in the selected signal path to actively disperse said dry powder into said exit flow path.

8. A dry powder inhaler according to claim 4, wherein said exit flow path is configured with an irregular shaped exit flow path to thereby facilitate turbulence is the air as it travels through said exit flow path.

9. A dry powder inhaler according to claim 8, wherein said air flow path has a width, and wherein said irregular shaped flow path comprises a baffle which is attached to said housing such that it extends a distance across the width of said air flow path.

10. A dry powder inhaler having an energy assisted dispersing system, comprising:

a housing configured to receive a dry powder package with at least one meted dose of dry powder, said housing having an airstream exit flow path;

a control system positioned in said housing configured to generate at least one operational excitation output signal having a plurality of associated frequencies, the operational excitation output signal comprising frequencies derived from an a priori flow analysis of the dry powder in the dry powder package, the frequencies being dependent on physiochemical properties and particle size of the dry powder; and

a power source operably associated with said control system.

11. A dry powder inhaler according to claim 10, wherein the computer readable program code configured with the at least one operational excitation output signal comprises computer readable program code with a look-up table of a range of operational excitation output pulses having associated frequencies, amplitudes and signal patterns associated therewith, each excitation output signal corresponding to a predetermined type of dry powder formulation.

12. A dry powder inhaler according to claim 10, the control system comprising a controller with computer readable program code configured to initiate the excitation output signal and further comprising computer readable computer program code for selecting the excitation output signal responsive to the dry powder package selected for inhalation.

13. A dry powder inhaler according to claim 10, further comprising a piezoelectric polymer member in the housing in communication with the control system, wherein, in operation, the control system is configured to transmit the excitation output signal to the piezoelectric polymer member to rapidly flex the piezoelectric member to thereby vibrate the dry powder during inhalation.

14. A dry powder inhaler according to claim 13, wherein the drug package is a multi-dose blister drug package with a plurality of spaced apart blisters, wherein the piezoelectric polymer member defines a portion of each blister, and wherein the control system is configured to transmit the excitation output signal to the piezoelectric polymer member associated with at least one blister during an inhalation.

15. A dry powder inhaler according to claim 13, wherein the piezoelectric polymer film is PVDF.

16. A dry powder inhaler according to claim 14, wherein the dry powder package holds a plurality of spaced apart blisters, at least pairs of blisters holding different dry powders, and wherein the control system is configured to transmit different excitation output signals to the at least pairs of blisters to dispense each of the different dry powders during an inhalation.

17. A dry powder inhaler having an energy assisted dispersing system, comprising:

a housing configured to receive a disposable dry powder package with at least one meted dose of dry powder, said housing having an airstream exit flow path;

a piezoelectric polymer member disposed in the housing configured to communicate with dry powder during an active inhalation cycle to vibrate the dry powder in the exit flow path; and

a control system positioned in said housing, said control system comprising;

a controller comprising computer program code configured to generate at least one operational excitation output signal having associated fundamental and subharmonic frequencies dependent on flow properties and particle size of the dry powder being dispensed during the active inhalation cycle; and

a power source operably associated with said control system.

18. A dry powder inhaler according to claim 17, wherein the computer readable program code configured with the at least one operational excitation output signal comprises computer readable program code with a look-up table of a range of operational excitation output pulses having associated frequencies, amplitudes and signal patterns associated therewith, each excitation output signal corresponding to a predetermined type of dry powder formulation.

19. A dry powder inhaler according to claim 17, the controller further comprising computer readable computer program code for selecting the excitation output signal responsive to the dry powder package selected for inhalation.

20. A dry powder inhaler according to claim 17, wherein the drug package is a multi-dose blister drug package with a plurality of spaced apart blisters, wherein the piezoelectric polymer member defines a portion of each blister, and wherein the control system is configured to transmit the excitation output signal to the piezoelectric polymer member associated with at least one blister during an inhalation.

21. A dry powder inhaler according to claim 17, wherein the piezoelectric polymer film is PVDF.

22. A method of actively assisting dispersion of a dry powder during inhalation using an inhaler, comprising:

transmitting an operational excitation output signal having a plurality of frequencies that are derived from a flow analysis of the dry powder in the inhaler to vibrate the dry powder during inhalation, the excitation signal frequencies being dependent on physiochemical properties and particle size of the dry powder; and

vibrating the dry powder held in an inhaler responsive to the transmitting step during inhalation.

23. A method according to claim 22, wherein the excitation signal frequencies comprise harmonic and subharmonic flow characteristic frequencies derived from the flow analysis of the inhalable dry powder.

24. A method according to claim 23, wherein the inhaler is configured to hold two different dry powders apart from each other before inhalation in the inhaler, and wherein the transmitting and vibrating steps are carried out to concurrently disperse both dry powders together to a user during inhalation, and wherein the harmonic and subharmonic flow characteristic frequencies are related to the physiochemical properties and particle sizes of the two different dry powders.

25. A new method according to claim 22, wherein the transmitting step transmits the excitation signal to a piezoelectric polymer member that comprises thin film PVDF with conductive portions.

26. A new method according to claim 22, wherein the transmitting and vibrating steps rapidly flex a piezoelectric polymer member generally upward and downward with the dry powder residing thereabove during at least a portion of an active inhalation cycle.

27. A dry powder inhaler having an energy assisted dispersing system, comprising:

a housing configured to receive at least one meted dose of dry powder, said housing having an airstream exit flow path;

a vibration system positioned in said housing configured to generate at least one excitation output signal comprising a plurality of dry powder-specific selected frequencies associated with physiochemical properties and particle size of the dry powder in the housing, wherein, in operation during inhalation, the vibration system is configured to apply the plurality of selected dry powder frequencies generally concurrently to the dry powder to disperse the dry powder to a user; and

a power source held by the housing operably associated with said vibration system.

28. A dry powder inhaler according to claim 27, wherein the selected frequencies are derived from an a priori flow analysis of the dry powder.

29. A dry powder inhaler according to claim 27, wherein the selected frequencies comprise at least one of the following flow characteristic frequencies of the dry powder:

(a) fundamental harmonic and (b) subharmonic frequencies.

30. A dry powder inhaler according to claim 28, wherein the selected frequencies are derived from a rotational drum flow analysis of the dry powder.

31. A dry powder inhaler according to claim 27, further comprising a dry powder containment system that releasably holds a plurality of different dry powders separate from each other for generally concurrent dispensing of the different dry powders.

32. A dry powder inhaler according to claim 31, wherein the vibration system is configured to generate the excitation signal using selected frequencies derived from individual flow analysis of the different dry powders.

33. A dry powder inhaler according to claim 32, wherein the vibration system comprises a piezoelectric polymer in communication with the different dry powders during active inhalation.