Dynamic particle size control for aerosolized drug delivery

• US 5,522,385 A
• Filed: 09/27/1994
• Issued: 06/04/1996
• Est. Priority Date: 09/27/1994
• Status: Expired due to Term

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Lloyd, Peter M., Schuster, Jeffrey A., Rubsamen, Reid M., Lloyd, Lester J.
• Primary Examiner(s): Funk, Stephen
• Assistant Examiner(s): RACITI, ERIC
• Application Number:
  US08/313,461
• Time in Patent Office: 616 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 128/201.13, 128/203.12, 128/203.14, 128/203.15, 128/203.16, 128/203.17, 128/203.23 , 128/203.24, 128/203.25, 128/203.26, 128/203.27, 128/203.15, 128/200.19, 128/204.17, 141/3, 222/394, 222/399
• US Class Current: 128/203.26
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• 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 16/108 before being humidified or mixed with a beneficial agent
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2205/52 with memories providing a history of measured variating parameters of apparatus or patient

Abstract

A device is provided which creates aerosolized particles by forcing a formulation of drug in a carrier through a nozzle (which nozzle may be in the form of a porous membrane) into a channel to a patient for inhalation. While in the channel energy is added to the particles in an amount sufficient to evaporate carrier and thereby reduce particle size. The amount of energy added can be adjusted depending on factors such as the particle size, the amount of the carrier to be evaporated, the water vapor content of the surrounding air and the composition of the carrier. Energy may be added in an amount sufficient to evaporate all carrier and thereby provide particles of dry powdered drug to patient which particles are uniform in size regardless of the surrounding humidity and smaller due to the evaporation of the carrier. Air drawn into the device by the patient may be drawn through a desiccator containing a desiccant which removes moisture from the air thereby improving evaporation efficiency when the carrier is water. Alternatively, water vapor may be introduced to the channel to saturate inhaled air thereby preventing evaporation of carrier and maintaining uniform particle size.

Claims

1. A method of drug delivery, comprising:

(a) providing a disposable porous membrane having pores with a diameter in the range of about 0.25 to about 6.0 microns;

(b) forming aerosolized particles of a formulation comprised of a carrier and a drug which particles have a diameter in the range of about 0.5 to about 12.0 microns by moving the formulation through the disposable porous membrane;

(c) adding energy to the aerosolized particles by actively heating air brought into contact with the particles;

(d) inhaling the particles into the lungs of a patient; and

(e) repeating (a)-(d) wherein a new disposable membrane is provided in each step (a) and used for each forming step (b).

2. The method of claim 1, comprising evaporating 50% or more of the carrier in the particles prior to the particles reaching the patient and wherein said adding occurs by actively heating air by moving air through a heated material which material is heated prior the patient'"'"'s inhalation.

3. The method of claim 1, comprising evaporating 80% or more of the carrier in the particles prior to the particles reaching the patient.

4. The method of claim 1, comprising evaporating substantially all carrier.

5. The method of claim 1, wherein the carrier is selected from the group consisting of water, ethanol and mixtures thereof.

6. The method of claim 1, wherein the porous membrane has from 10 to 10,000 pores over an area of from about 1 mm² to about 1 cm².

7. The method of claim 1, further comprising:

actively heating the formulation prior to moving the formulation through the porous membrane.

8. The method of claim 1, wherein the carrier is comprised of water.

9. The method of claim 8, further comprising:

providing a channel having a first opening into which air is inhaled, a second opening from which a patient withdraws air and a third opening through which the aerosolized particles enter the channel; and

providing a desiccator in the channel at a point after the first opening and prior to the second and third openings in a direction of flow from the first to second to the third opening.

10. The method of claim 9, wherein the desiccator is selected from the group consisting of P₂ O₅, Mg(ClO₄), KOH, H₂ 5O₄, NaOH, CaO, CaCl₂, ZnCl₂, and CaSO₄.

11. A method of drug delivery, comprising:

providing a volume of air;

inhaling the volume of air through a desiccator into a channel wherein the desiccator absorbs water vapor from air to obtain a volume of dried air;

providing a formulation comprised of a pharmaceutically active drug and a water carrier;

moving the formulation through pores of a porous membrane into the volume of dried air in a manner so as to form aerosolized particles and the aerosolized particles are drawn into the channel; and

continuing to inhale so as to draw the aerosolized particles and dried air into the lungs of a patient.

12. The method of claim 11, wherein the desiccator is selected from the group consisting of P₂ O₅, Mg(ClO₄), KOH, H₂ 5O₄, NaOH, CaO, CaCl₂, ZnCl₂, and CaSO₄.

13. The method of claim 11, further comprising:

adding energy to the volume of dried air so as to increase the ability of the air to held a higher concentration of water vapor.

14. A method of drug delivery, comprising:

inhaling air into a channel which channel leads to an inhaling patient;

moving formulation through pores of a disposable porous membrane wherein the pores have a diameter of about 0.25 to about 6.0 microns in a manner so as to form aerosolized particles having a diameter in the range of from about 0.5 to about 12.0 microns wherein the formulation is comprised of a pharmaceutically active drug and a water carrier and the aerosolized particles are drawn in to the channel;

introducing water in the form of water vapor or aerosolized water particles into the air in the channel; and

continuing to inhale so as to draw the aerosolized particles into the lungs of the patient;

wherein the water is substantially pure and is introduced in an amount sufficient to substantially saturate air inhaled into the channel and thereby substantially eliminate evaporation of water carrier from the aerosolized particles.

15. A method of drug delivery, comprising:

heating a formulation wherein the formulation is comprised of a pharmaceutically active drug and a water carrier;

moving the heated formulation through a nozzle in a manner so as to form aerosolized particles;

adding energy to the aerosolized articles by actively heating air surrounding the particles;

inhaling air into a channel which leads to the aerosolized particles and to an inhaling patient wherein the inhaled air is drawn through a desiccator to the channel wherein the desiccator absorbs water vapor from air; and

inhaling the particles into the lungs of a patient.

16. A drug delivery device, comprising:

a channel having a first opening into which air can be inhaled, a second opening from which a patient can withdraw air and a third opening through which aerosolized particles enter the channel;

a container having a formulation therein;

a means for applying physical force to the formulation upon actuation;

a disposable porous membrane through which the formulation is forced through the membrane having pores with a diameter of about 0.25 to about 6.0 microns;

an air-heating device which adds energy to air inhaled into the channel; and

a means for moving disposable membranes into a drug release position for use and out of the drug release position after use.

17. The drug delivery device of claim 16, further comprising:

a desiccator positioned in the channel at a point after the first opening and prior to the second and third in a direction of flow from the first opening to the second and third opening;

wherein the desiccator absorbs water vapor from air;

wherein the device is a hand-held self-contained device having a total weight of 1 kilogram or less.

18. The drug delivery device of claim 16, wherein the means for applying physical force to the formulation is selected from the group consisting of a piston and a vibration device.