Phospholipid-based powders for inhalation

• US 20040105820A1
• Filed: 07/08/2003
• Published: 06/03/2004
• Est. Priority Date: 09/29/1997
• Status: Abandoned Application

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Novartis Pharma AG (Novartis Ag)
• Inventors: Weers, Jeffry G., Tarara, Thomas E., Clark, Andrew
• Application Number:
  US10/616,448
• Publication Number:
  US 20040105820A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods for inhalation are provided. The formulations for inhalation are engineered to be highly dispersible and provide rapid absorption of the active agent so delivered, as well as substantially independent emitted doses and lung deposition as functions of device resistance and inspiratory flow rates, respectively. The present invention also provides reductions in the flow rate dependence in lung deposition and improvements in patient reproducibility.

Claims

1. A method for inhalation of a dry powder drug comprising:

providing a dry powder drug composition comprising particles comprising a lipid matrix and a particle size of 1-30 microns, mass median aerodynamic diameter of less than 5 microns, and bulk density of less than 0.5 g/cm³;

loading the composition into a passive dry powder inhaler; and

inhaling the drug composition from the inhaler resulting in an emitted dose substantially independent of device resistance and lung deposition substantially independent of inhalation flow rate.

2. A method according to claim 1 wherein the emitted dose is at least 60%.

3. A method according to claim 2 comprising an emitted dose of at least 80%.

4. A method according to claim 1 comprising a FPF_4+F of at least 60%.

5. A method according to claim 1 wherein the lipid comprises a phospholipid selected from the group consisting of dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine, diarachidoylphosphatidylcholine dibehenoylphosphatidylcholine, diphosphatidyl glycerol, short-chain phosphatidylcholines, long-chain saturated phosphatidylethanolamines, long-chain saturated phosphatidylserines, long-chain saturated phosphatidylglycerols, and long-chain saturated phosphatidylinositols.

6. A method according to claim 1 wherein the inhaler comprises a resistance of less than 0.60 (cmH₂O)^1/2/L min⁻

1.

7. A method according to claim 6 wherein the inhaler comprises a resistance within the range of 0.01-0.30 (cmH₂O)^1/2/Lmin⁻

1

8. A method of claim 1 wherein the inhalation flow rate is less than about 90 L/min.

9. A method of claim 8 wherein the inhalation flow rate is within the range of about 10-60 L/min.

10. A method of claim 9 wherein the inhalation flow rate is within the range of 12-45 L/min.

11. A method of claim 1 wherein the lung deposition is greater than 25%.

12. A method according to claim 1 wherein the lung deposition is greater than 30%.

13. A method according to claim 1 wherein the lung deposition is greater than 50%.

14. A method according to claim 1 wherein the drug is selected from the group consisting of budesonide, tobramycin sulfate, leuprolide acetate, Amphotericin B, and PTH.

15. A method of claim 1 wherein the powder comprises hollow porous microparticles.

16. A method for inhalation of a dry powder drug comprising:

providing a dry powder drug composition comprising a hydrophobic active agent, said composition comprising particles comprising a lipid matrix and a particle size of 1-30 microns, mass median aerodynamic diameter of less than 5 microns, and bulk density of less than 0.5 g/cm³;

loading the composition into a passive dry powder inhaler;

inhaling the drug composition from the inhaler in order to achieve a Tmax within 15 minutes of the inhalation.

17. A method according to claim 16 wherein the active agent is amphotericin B.

18. A method according to claim 16 wherein the active agent is budesonide.

19. A method according to claim 18 wherein T max is achieved within 10 minutes of the inhalation.

20. A method according to claim 16 wherein the lipid comprises a phospholipid selected from the group consisting of dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine, diarachidoylphosphatidylcholine dibehenoylphosphatidylcholine, diphosphatidyl glycerol, short-chain phosphatidylcholines, long-chain saturated phosphatidylethanolamines, long-chain saturated phosphatidylserines, long-chain saturated phosphatidylglycerols, and long-chain saturated phosphatidylinositols.