Intrapulmonary delivery of aerosolized formulations

• US 5,709,202 A
• Filed: 05/21/1993
• Issued: 01/20/1998
• Est. Priority Date: 05/21/1993
• Status: Expired due to Fees

• Current Assignee: Intel Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Lloyd, Peter M., Lloyd, Lester John, Rubsamen, Reid M.
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US08/065,660
• Time in Patent Office: 1,705 Days
• Field of Search: 128/200.14, 128/200.16, 128/200.19, 128/200.22, 128/203.12, 128/203.15, 128/203.21, 128/204.21, 128/204.23, 128/200.23
• US Class Current: 128/200.14
• CPC Class Codes: A61J 1/035 Blister-type containers blisters in general B65D75/36
• CPC Class Codes: A61J 1/1418 Threaded type
• CPC Class Codes: A61J 7/04 Arrangements for time indication or reminder for taking medicine, e.g. programmed dispensers
• CPC Class Codes: A61J 7/0418 with electronic history memory
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/001 using ultrasonic means
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0043 Non-destructive separation of the package, e.g. peeling
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0055 the used dosages being coiled
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/40 Respiratory characteristics
• CPC Class Codes: B65D 81/32 for packaging two or more different materials which must be maintained separate prior to use in admixture containers with removable or destructible partitions B65D25/08 ; closures combined with auxiliary containers B65D51/28; in aerosol containers B65D83/682; amalgam capsules A61C5/66; containers for pharmaceutical purposes A61J1/20, A61M5/19; medical syringes A61M3/005, resin cartridges for grouting anchoring-bolts in mines E21D20/026

Abstract

Liquid, flowable formulations including aqueous formulations of a pharmaceutically active drug are packaged in individual dosage unit containers which containers are interconnected to form a cellular array designed to be integrated into a dispensing device capable of individually opening dosage unit containers and aerosolizing the contents through a nozzle for delivery to a patient. The cellular array is comprised of a plurality of containers with each container having an opening(s) thereon from which a drug-containing formulation may be aerosolized. The dispensing device is a hand-held, self-contained, portable device comprised of a means for removing covers from the containers and automatically dispensing the formulation from individual containers, preferably in response to a signal obtained as a result of measuring the inspiratory flow of a patient. The cellular array is loaded into the dispensing device to form a system which can be used in a method of delivering drugs to a patient via the intrapulmonary route. In a preferred embodiment each container includes an opening covered by a membrane having a plurality of pores therein wherein the pores have a diameter of about 0.5 microns to 50 microns and the dispensing device includes a vibrating device which creates a vibration frequency such that formulation forced through the pores is aerosolized to particles having a diameter of about 1 micron to 100 microns.

Claims

1. A hand-held, self-contained drug delivery system for intrapulmonary delivery of drugs, comprising:

a cellular array comprised of a plurality of interconnected individual containers with each container having a disposable membrane thereon wherein the membrane includes a plurality of pores therein which pores are provided in a pore density of about 1×

10⁵ to about 1×

10⁸ pores/cm² and which have a diameter in the range of about 0.5 to about 5 microns the container having therein a liquid formulation comprising a pharmaceutically active drug wherein each container includes a wall which is collapsible by the application of sufficient pressure to force the liquid formulation out of the container and form particles sufficiently small such that a patient can inhale the particles;

a transport mechanism for successively moving each individual container into a drug release position for release of the drug therefrom;

a mechanical mechanism for applying force to the collapsible wall of an individual container upon actuation;

a housing interconnecting the transport mechanism and mechanical mechanism, while allowing the cellular array to be moved so that successive containers on the cellular array are placed in the drug release position; and

an instrument for measuring inspiratory flow and sending an electrical signal as an indication of the measurement; and

a microprocessor programmed to receive, analyze and store the electrical signal of the instrument for measuring flow and upon receipt of a threshold signal value sending an actuation signal to the mechanical mechanism for applying force.

2. The drug delivery system of claim 1, further comprising:

a vibrating device for vibrating each membrane at frequency such that when formulation is forced from the pores the formulation is aerosolized.

3. The drug delivery system of claim 2 wherein the mechanical mechanism is in the form of a piston and the vibrating device is in the piston.

4. The drug delivery system of claim 1, wherein the membrane has a density in the range of 0.5 to 2.0 mg/cm² and a thickness in the range of about 2 to about 20 microns.

5. The drug delivery system of claim 4, wherein the membrane has a thickness in the range of 8 to 12 microns.

6. A hand-held, self-contained drug dispersing dosage unit for intrapulmonary delivery of drugs, comprising:

a first disposable container having a plurality of openings thereof with each opening having a diameter of about 0.5 micron to about 5 microns, a pharmaceutically active drug therein and an opening allowing inflow; and

a second disposable container having at least one wall with a portion thereon designed to rupture upon the application of pressure which portion is positioned adjacent to the opening in the first container and at least one wall collapsible in a manner so as to increase the pressure of the contents in the second container in an amount sufficient to rupture said one wall portion.

7. The dosage unit of claim 6, wherein the pharmaceutically active drug is a respiratory drug.

8. The dosage unit of claim 6, wherein the respiratory drug is selected from the group consisting of a bronchodilator and a non-steroidal anti-inflammatory drug.

9. The dosage unit of claim 6, wherein the pharmaceutically active drug is a drug which has a systemic effect.

10. The dosage unit of claim 9, wherein the drug which has a systemic effect is a protein.

11. The dosage unit of claim 10, wherein the protein is DNAse.

12. The drug delivery system of claim 6, wherein the membrane has a density in the range of 0.5 to 2.0 mg/cm² and a thickness in the range of about 2 to about 20 microns.

13. The drug delivery system of claim 12, wherein the membrane has a thickness in the range of 8 to 12 microns.