PHOSPHOLIPID-BASED POWDERS FOR DRUG DELIVERY

• US 20090047358A1
• Filed: 10/24/2008
• Published: 02/19/2009
• Est. Priority Date: 05/10/2000
• Status: Active Grant

• Current Assignee: Ernest G. Schutt, Jean G. Riess, Jeffry G. Weers, Luis A. Dellamary, Thomas E. Tarara
• Original Assignee: Ernest G. Schutt, Jean G. Riess, Jeffry G. Weers, Luis A. Dellamary, Thomas E. Tarara
• Inventors: WEERS, Jeffry G., Riess, Jean G., Schutt, Ernest G., Dellamary, Luis A., Tarara, Thomas E.
• Granted Patent: US 8,709,484 B2
• Time in Patent Office: Days
• US Class Current: 424/502
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/0082 Lung surfactant, artificial mucus
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• 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 2205/3306 Optical measuring means
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Phospholipid based powders for drug delivery applications are disclosed. The powders comprise a polyvalent cation in an amount effective to increase the gel-to-liquid crystal transition temperature of the particle compared to particles without the polyvalent cation. The powders are hollow and porous and are preferably administered via inhalation.

Claims

1. A method for producing a phospholipid particulate composition comprising:

adding a polyvalent cation to a formulation comprising a phospholipid;

drying said formulation to form a dry particulate composition comprising hollow and porous particles.

2. A method according to claim 1 wherein the particulate composition comprises particles having a mass median diameter of less than 20 microns.

3. A method according to claim 2 wherein the mass median diameter is within 0.5-5 microns.

4. A method according to claim 1 wherein the particles comprise an aerodynamic diameter of less than 10 microns.

5. A method according to claim 4 wherein the aerodynamic diameter is within 0.5-5 microns.

6. A method according to claim 1 wherein the drying step is performed by spray drying.

7. A method according to claim 6 wherein the spray drying process comprises adding a blowing agent to the feedstock.

8. A method according to claim 7 wherein the feedstock comprises a colloidal solution or suspension.

9. A method according to claim 8 wherein the polyvalent cation is added to the feedstock at a molar ratio of cation:

phospholipid of 0.25-1.0

10. A method according to claim 9 wherein the polyvalent cation is added to the feedstock as calcium chloride.

11. A method according to claim 1 wherein the formulation further comprises an active agent.

12. A method according to claim 11 wherein the active agent is a therapeutic agent.

13. A method according to claim 12 wherein the therapeutic agent is selected from the group consisting of nicotine, human growth hormone, parathyroid hormone, leuprolidde, budesonide, tobramycin, albuterol, insulin, interferon alpha, interferon beta, amphotericin, fluticasone, salmeterol, formoterol, and salts thereof.

14. A method according to claim 13 wherein the therapeutic agent is budesonide.

15. A method according to claim 13 wherein the therapeutic agent is tobramycin.

16. A method according to claim 13 wherein the therapeutic agent is albuterol.

17. A method according to claim 13 wherein the therapeutic agent is insulin.

18. A method according to claim 13 wherein the therapeutic agent is interferon alpha.

19. A method according to claim 13 wherein the therapeutic agent is interferon beta.

20. A method according to claim 13 wherein the therapeutic agent is amphotericin.