PRESERVATIVE FREE INSULIN FORMULATIONS AND SYSTEMS AND METHODS FOR AEROSOLIZING

• US 20110168170A1
• Filed: 01/11/2011
• Published: 07/14/2011
• Est. Priority Date: 01/12/2010
• Status: Active Grant

• Current Assignee: Aerami Therapeutics, Inc. (Dance Biopharm Holdings, Inc.)
• Original Assignee: Dance Pharmaceuticals, Inc.
• Inventors: Kuo, Mei-chang, Patton, Ryan S., Patton, John S., Ivri, Yehuda
• Granted Patent: US 9,180,261 B2
• Time in Patent Office: Days
• US Class Current: 128/200.14
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• 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 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• 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 2202/0468 non-physiological
• CPC Class Codes: A61M 2205/3334 Measuring or controlling the flow rate
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/587 Lighting arrangements
• CPC Class Codes: A61M 2209/045 for filling, e.g. for filling reservoirs
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics

Abstract

One embodiment describes an insulin formulation that is specifically adapted for aerosolization. The formulation comprises a major amount of water and a minor amount of insulin. Further, the formulation is preservative free, without meta-cresol, cresol or phenol, to permit the formulation to be aerosolized using a vibrating aperture plate without substantial foaming of the insulin formulation.

Claims

1. An insulin formulation specifically adapted for aerosolization, the formulation comprising:

a major amount of water;

a minor amount of insulin;

wherein the formulation is preservative free to permit the formulation to be aerosolized using a vibrating aperture plate without substantial foaming of the insulin formulation.

2. An insulin formulation as in claim 1, wherein the insulin has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

3. An insulin formulation as in claim 1, wherein the water comprises in volume about 99.8% to about 97.0%, and the human insulin comprises in volume about 0.2% to about 3.0%.

4. An insulin formulation as in claim 1, wherein the formulation does not include meta-cresol, cresol or phenol.

5. An insulin formulation specifically adapted for aerosolization, the formulation consisting essentially of:

a major amount of water;

a minor amount of insulin;

a minor amount of HCl; and

a minor amount of NaOH;

wherein the formulation is preservative free such that the formulation may be aerosolized using a vibrating aperture plate without substantial foaming of the formulation.

6. An insulin formulation as in claim 5, wherein the insulin has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

7. An insulin formulation as in claim 5, wherein the water comprises in volume about 99.8% to about 970%, the human insulin comprises in volume about 0.2% to about 3.0%.

8. An insulin formulation specifically adapted for aerosolization, the formulation comprising:

a major amount of water;

a minor amount of insulin;

wherein the formulation is capable of being aerosolized as a spray using a vibrating aperture plate having a plurality of apertures that vibrates at a frequency in the range from about 50 kHz to about 150 kHz, and wherein the amount of the insulin formulation has a volume of up to about 200 μ

L, and wherein the time to aerosolize the 97% is less than about 22 seconds.

9. An insulin formulation as in claim 8, wherein the insulin formulation does not contain a preservative such that the formulation may be aerosolized using the vibrating aperture plate without substantial foaming of the formulation.

10. An insulin formulation as in claim 8, wherein the insulin has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

11. A method for aerosolizing an insulin formulation, the method comprising:

providing an insulin formulation comprising a major amount of water, and minor amounts of insulin, HCl and NaOH;

supplying an amount of the insulin formulation to a rear side of an aperture plate having a plurality of apertures;

vibrating the aperture plate while the insulin formulation is at the rear side, wherein vibration causes the supplied insulin to be ejected from a front side of the aperture plate as an aerosolized spray without substantial foaming of the insulin formulation.

12. A method as in claim 11, wherein at least about 97% of the formulation is ejected.

13. A method as in claim 12, wherein the amount of the insulin formulation has a volume of up to about 100 μ

L, and wherein the time to aerosolize to at least about 97% is less than about 11 seconds.

14. A method as in claim 11, further comprising vibrating the aperture plate with an amplitude that is less than about 2 μ

m.

15. A method as in claim 11, wherein the aerosolized spray comprises aerosolized droplets having a mean size in the range from about 3 μ

m to about 8 μ

m.

16. A method as in claim 11, wherein the formulation has less than about 3% converted to foam when vibrating the aperture plate.

17. A method as in claim 11, wherein the insulin has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

18. A method as in claim 11, wherein the aperture plate has apertures having a size in the range from about 3 μ

m to 8 μ

m, and is vibrated at a frequency in the range from about 50 kHz to about 150 kHz.

19. An aerosolization system, comprising:

an inhaler comprising a housing defining a mouthpiece, an aerosol generator disposed in the housing, wherein the aerosol generator comprises a vibratable membrane having a front face and a rear face, and a vibratable element used to vibrate the membrane;

a container containing a volume of an insulin formulation consisting essentially of a major amount of water and a minor amount of insulin, wherein the formulation is preservative free such that the formulation may be aerosolized using a vibrating aperture plate without substantial foaming of the formulation.

20. A system as in claim 20, wherein the insulin has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

21. A system as in claim 20, wherein the aperture plate has apertures having a size in the range from about 3 μ

m to 8 μ

m.

22. A system as in claim 20, wherein the vibratable membrane is configured to vibrate with a frequency that is less than about 2 μ

m.