Pharmaceutical composition for pulmonary delivery

• US 20030152523A1
• Filed: 12/26/2002
• Published: 08/14/2003
• Est. Priority Date: 02/08/2000
• Status: Abandoned Application

• Current Assignee: Kings College London (University of London)
• Original Assignee: Kings College London (University of London)
• Inventors: Zeng, Xian Ming, Martin, Gary Peter
• Application Number:
  US10/203,266
• Publication Number:
  US 20030152523A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/569 substituted in position 17 alpha, e.g. ethisterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• 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 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

A dry particulate pharmaceutical composition for pulmonary administration is prepared by spray-drying a hydrophobic active agent (e.g. declomethasone dipropionate) with a small quantity of pharmaceutically acceptable hydrophilic polymer (e.g. poly (vinyl) alcohol). This mitigates aggregation of the particles of active agent, which otherwise limits the desirable find particles dose available.

Claims

1. A particulate pharmaceutical composition for pulmonary delivery, which comprises a hydrophobic pharmaceutically active agent which has been spray-dried with a small quantity of a pharmaceutically acceptable hydrophilic polymer to form spray-dried particles.

2. A composition according to claim 1 wherein the ratio of active agent to hydrophilic polymer is in the range 1:

0.05 to 1;

0.1 in the spray-dried particles.

3. A composition according to any preceding claim wherein the hydrophilic polymer is poly(vinyl)alcohol.

4. A composition according to claim 3 wherein the poly(vinyl)alcohol has a molecular weight of 9000 to 10,000.

5. A composition according to any preceding claim wherein the volume mean diameter of the spray-dried particles is from 1 to 6.4 μ

m.

6. A composition according to any preceding claim wherein the pharmaceutically active agent is a corticosteroid.

7. A composition according to claim 6 wherein the corticosteroid is beclomethasone dipropionate.

8. A composition according to claim 6 wherein the corticosteroid is budesonide or fluticosone dipropionate.

9. A composition according to any of claims 1 to 5 wherein the pharmaceutically active agent is a beta 2 agonist.

10. A composition according to claim 9 wherein the beta 2 agonist is salmeterol or salbutamol.

11. A composition according to any of claims 1 to 5 wherein the pharmaceutically active agent is an anticholinergic drug.

12. A composition according to claim 11 wherein the anticholinergic drug is ipratropium bromide.

13. A composition according to any of claims 1 to 5 wherein the pharmaceutically active agent is a leukotriene.

14. A composition according to any of claims 1 to 5 wherein the pharmaceutically active agent is a peptide, an antisense therapeutic or a gene therapeutic.

15. A composition according to claim 14 wherein the peptide is insulin or calcitonin.

16. A composition according to any preceding claim, which further comprises a pharmaceutically acceptable carrier.

17. A composition according to claim 16 wherein the carrier is lactose.

18. A composition according to claim 16 or 17 wherein the carrier has a specific size range of 63-90 μ

m.

19. A composition according to any of claims 16 to 18 wherein the ratio of spray-dried particles to carrier is substantially 1:

67.5 w/w.

20. A composition according to any of claims 16 to 19 wherein the hydrophilic polymer is 0.073 to 0.146% of the total composition weight.

21. A method of producing a particulate pharmaceutical composition, which comprises spray drying a hydrophobic pharmaceutically active agent with a small quantity of a pharmaceutically acceptable hydrophilic polymer to form spray-dried particles.

22. A method according to claim 21 wherein active agent particles are dispersed in a solution of the hydrophilic polymer, prior to spray drying.

23. A particulate pharmaceutical composition for pulmonary delivery, which comprises a hydrophobic pharmaceutically active agent which has been spray-dried with a small quantity of a pharmaceutically acceptable hydrophilic polymer;

or conversely a hydrophilic pharmaceutically active agent which has been spray-dried with a small quantity of a pharmaceutically acceptable hydrophobic polymer;

to form spray-dried particles.