Carrier particles for use in dry powder inhalers

• US 6,521,260 B1
• Filed: 10/06/2000
• Issued: 02/18/2003
• Est. Priority Date: 01/31/1995
• Status: Expired due to Term

• Current Assignee: Vectura Limited (Vectura Group Ltd.)
• Original Assignee: Vectura Limited (Vectura Group Ltd.)
• Inventors: Staniforth, John Nicholas
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): DeWitty, Robert M
• Application Number:
  US09/680,863
• Time in Patent Office: 865 Days
• Field of Search: 514/423, 424/452, 424/45, 424/490
• US Class Current: 424/490
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• 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 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators

Abstract

A powder for use in a dry powder inhaler includes active particles and carrier particles for carrying the active particles. The powder further includes additive material (4) on the surfaces of the carrier particles to promote the release of the active particles from the carrier particles on actuation of the inhaler. The powder is such that the active particles are not liable to be released from the carrier particles before actuation of the inhaler. The inclusion of additive material (4) in the powder has been found to give an increased respirable fraction of the active material.

Claims

1. A powder for use in a dry powder inhaler, the powder comprising active particles and carrier particles for carrying the active particles, the powder further comprising additive material comprising magnesium stearate, the additive material being on the surfaces of the carrier particles and the amount of additive material is such that the active particles are not liable to be released from the carrier particles before the actuation of the inhaler.

2. A powder according to claim 1 which comprises less than 1.5% additive material based on the weight of the powder.

3. A powder according to claim 1 in which the additive material consists essentially of magnesium stearate.

4. A powder according to claim 1 in which the additive material is in the form of particles.

5. A powder according to claim 1 in which the additive particles form a discontinuous covering on the surfaces of the carrier particles.

6. A powder according to claim 1 in which the additive material is in the form of particles having a diameter of less than 150 μ

m.

7. A powder as claimed in claim 1 in which the additive material is in the form of particles having a mass median diameter of less than 10 μ

m.

8. A powder as claimed in claim 1 in which substantially all (by weight) of the carrier particles have a diameter which lies between 20 μ

m and 1000 μ

m.

9. A powder according to claim 1 wherein the carrier particles are comprised of one or more crystalline sugars.

10. A powder according to claim 1 wherein the carrier particles are particles of lactose.

11. A powder according to claim 1 wherein the powder consists of not less than 0.1% by weight of additive material based on the weight of the carrier particles.

12. A powder according to claim 1 further comprising a fraction of small grains.

13. A powder according to claim 1 wherein the small grains are of the same composition as the carrier particles.

14. A powder according to claim 1 wherein the mass median diameter of the active particles is not more than 10 μ

m.

15. A powder according to claim 1 wherein the active particles include a β

₂-agonist.

16. A powder according to claim 1 wherein the active particles include salbutamol, a salt of salbutamol or a combination thereof.

17. A powder according to claim 1 wherein the active particles include beclomethasone dipropionate.

18. A powder according to claim 1 wherein the active particles include a peptide or a polypeptide.

19. A powder according to claim 1 wherein the active particles include a carbohydrate.

20. A method of producing a powder for use in dry powder inhalers, the method including the steps of

(a) mixing carrier particles of a size suitable for use in a dry powder inhaler with additive material comprising magnesium stearate such that at least some of the additive material becomes attached to the surfaces of the carrier particles;

and

(b) mixing the carrier particles with active particles such that active particles adhere to the surfaces of the carrier particles and/or the additive material,

wherein the amount of additive material is such that the active particles are not liable to be released from the carrier particles before actuation of the inhaler.

21. A method according to claim 20 which includes a milling step.

22. A method according to claim 20 wherein the milling step is performed in a ball mill.

23. A method as claimed in claim 20 in which the milling step is performed in a re-circulated low fluid energy mill.

24. A method according to claim 20 wherein the milling step dislodges small grains from the surfaces of the carrier particles, without substantially changing the size of the carrier particles.

25. A method according to claim 20 wherein the mixing step a) is prior to the milling step.