PULSE DRUG NEBULIZATION SYSTEMS, FORMULATIONS THEREFORE, AND METHODS OF USE

• US 20080230053A1
• Filed: 09/14/2007
• Published: 09/25/2008
• Est. Priority Date: 09/15/2006
• Status: Abandoned Application

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Traber, Daniel L., Enkhbaatar, Perenlei, Kraft, Edward R., Kulp, Gabriela A.
• Application Number:
  US11/855,870
• Publication Number:
  US 20080230053A1
• Time in Patent Office: Days
• US Class Current: 128/200.23
• CPC Class Codes: A61M 11/04 operated by the vapour pressure of the liquid to be sprayed or atomised air-humidification, e.g. "room humidifiers" F24F6/00
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/002 with air flow regulating means
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• 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 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 16/06 Respiratory or anaesthetic masks
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: B05B 7/066 with an inner liquid outlet surrounded by at least one annular gas outlet
• CPC Class Codes: B05B 7/0876 to form parallel jets constituted by a liquid or a mixture containing a liquid B05B7/0884, B05B7/0892 take precedence
• CPC Class Codes: B05B 7/0892 the outlet orifices for jets constituted by a liquid or a mixture containing a liquid being disposed on a circle

Abstract

Liquid nebulizer apparatus, systems, and formulation compositions, as well as systems for the nebulized, aerosol delivery of such compositions, for the administration and insufflation of medicinal aerosols into the pulmonary system of a mammal are described. The nebulizing apparatus and system can effectively aerosolize a variety of viscosities of medicinal liquid drug carriers, including those made up of oil, water, or emulsions of oil and water. Drugs dissolved or suspended in the compositions and formulations described and adapted for use herein are not damages or denatured by the nebulization process when the nebulizer described is used. Further, the nebulization system itself can be adapted for use with both mechanically assisted pulmonary ventilation systems as well as hand-held inhalers and nose/mouth face masks for use in pulmonary drug delivery.

Claims

1. A nebulization system comprising:

a nozzle;

an outer gas-delivery tube; and

an inner microchannel delivery tube having a central fluid channel;

wherein the outer delivery tube is concentrically configured around the inner delivery tube, such concentric configuration forming an annular intermediate space between the two tubes, and

wherein the intermediate air space between the two tubes is the free air opening value, the value of which is the internal diameter of the outer gas-delivery tube minus the total inside diameter of the inner microchannel delivery tube.

2. The nebulization system of claim 1, wherein the nozzle has an air volume to nebulized droplet volume ratio less than about 60,000:

1.

3. The nebulization system of claim 1, wherein the value of the intermediate air space between the two tubes ranges from about 0.00000259 in² to about 0.001 in².

4. The nebulization system of claim 1, wherein the outer gas delivery tube has an inner diameter ranging from about 0.01 inches to about 0.05 inches.

5. The nebulization system of claim 1, wherein the inner microchannel delivery tube has an outer diameter ranging from about 0.01 inches to about 0.04 inches.

6. The nebulization system of claim 1, wherein the system is capable of producing aerosol droplets of compositions comprising a fatty acid or lipids having particle sizes ranging from about 2 μ

m to about 12 μ

m.

7. A pulmonary drug delivery system capable of nebulizing a composition comprising a water-insoluble or substantially water-insoluble drug and a fatty acid or lipid, the system comprising:

a reservoir for containing the drug composition;

a reservoir for containing a propellant gas;

a mechanical control valve capable of regulating the flow of the propellant gas and the drug composition; and

a nebulizing nozzle adapted to receive both the drug composition and the propellant gas;

wherein the nebulizing nozzle can produce aerosol droplets having a particle size ranging from about 2 μ

m to about 12 μ

m in median mass aerodynamic size.

8. The pulmonary drug delivery system of claim 7, further comprising an assembly fitted into the air stream of a mammalian patient.

9. The pulmonary drug delivery system of claim 7, wherein the nebulizing nozzle can produce aerosol droplets having a particle size ranging from about 2 μ

m to about 5 μ

m.

10. A non-aqueous medicinal aerosol composition, comprising:

a therapeutically effective amount of a pulmonary medicament or a derivative, metabolite, solvate, hydrate, prodrug, or polymorph thereof;

a lipid or fatty acid; and

a fluid propellant carrier.

11. The composition of claim 10, wherein the pulmonary medicament is gamma-tocopherol.

12. The medicament of claim 11, wherein the gamma-tocopherol is in either the d-, l-, or dl-conformation, or a combination thereof.

13. The composition of claim 10, wherein the therapeutically effective amount of the pulmonary medicament ranges from about 1% (w/w) to about 99% (w/w).

14. The composition of claim 10, wherein the lipid or fatty acid is present in an amount ranging from about 1% (w/w) to about 99% (w/w).

15. The composition of claim 10, further comprising an antioxidant for use in the preparation of a medicament for the treatment of disease or disorder of the pulmonary system, including but not limited to acute lung injury.

16. The composition of claim 15, wherein the antioxidant is a vitamin selected form the group consisting of Vitamin E, Vitamin C, riboflavin, niacin, vitamin K3, ascorbic acid, coenzyme-Q and β

-carotene.

17. The composition of claim 10, wherein the fatty acid is selected from the group consisting of flax seed oil, sunflower oil, saffron oil, and canola oil.

18. The composition of claim 10, further comprising a surfactant.

19. The medicinal composition of claim 10, wherein the therapeutically effective amount ranges from about 1 mg/kg/d to about 1,000 mg/kg/d.

21. The drug nebulizing apparatus of claim 19, wherein the drug formulation is in the form of a mixture, a solution, a suspension, or an emulsion.

22. The drug nebulizing apparatus of claim 19, wherein the face mask is capable of being fit to the patient'"'"'s nose, mouth, or both the nose and the mouth.

23. The drug nebulizing apparatus of claim 19, wherein the droplets range in size from about 2 μ

m to about 10 μ

m.

24. The drug nebulizing apparatus of claim 22, wherein the droplets range in size from about 2 μ

m to about 5 μ

m.

25. The drug nebulizing apparatus of claim 19, wherein the nebulizing nozzle comprises a fluid micro-tube with an air delivery tube capable of nebulizing a fluid from the micro-tube into droplets into droplets sized for inhaled drug delivery.

20. A drug nebulizing apparatus adapted for pulmonary inhalation and delivery of aerosolized medicaments into a mammalian patient, the apparatus comprising:

a reservoir containing a drug formulation; and

a nebulizing nozzle adapted to be fit to a breathing circuit and further attached to a face mask;

wherein the nebulizing nozzle produces aerosolized droplets sized for pulmonary, inhaled drug delivery of the drug formulation.