Patent EA-000352-B1 (EA)
Title: Carrier particles for use in a dry powder inhaler
Inventor: STANIFORTH JOHN NICHOLAS
IPC: A61K9/00
Filed: 1996-01-31
Abstract: 1. A powder, the powder including active particles and for carrying the active particles, the powder further including additive material en the surfaces of the carrier particles to promote the release of the active particles from the carrier particles on activation of the inhaler, the additive material including an amino acid or a derivative thereof. 2. A powder according to Claim 1, wherein the amino acid is leucine. 3. A powder according to Claim 1 or Claim 2, wherein the powder includes not more than 4% by weight of additive material based on the weight of the powder. 4. A powder according to Claim 3, wherein the powder includes not more than 2% by weight of additive material based on the weight of the powder. 5. A powder according to any of Claims 1 to 4, wherein the additive material is in the form of particles. 6. A powder for use in a dry powder inhaler, the powder including active particles and carrier particles for carrying the active particles, the powder further including additive material on the surfaces of the carrier particles to promote the release of the active particles from the carrier particles on actuation of the inhaler, chosen from a group consisting of amino acid and derivatives thereof, peptides, polypeptides and derivatives thereof, surface active materials., anti-adherent materials, anti-friction agents and additive material, the powder being such that the active particles are not liable to be released from the carrier particles before actuation of the inhaler. 7. A powder according to Claim 6 wherein the powder includes not more than 5% by weight of additive material based on the weight of the powder. 8. A powder according to Claim 7 wherein the powder includes not more than 2% by weight of additive material based on the weight of the powder. 9. A powder according to any of Claims 6 to 8 wherein the carrier particles are comprised of one or more crystalline sugars. 10. A powder according to Claim 9 wherein the carrier particles are particles of lactose. 11. A powder according to any of Claims 6 to 10 wherein substantially all (by weight) of the carrier particles have a diameter, which lies between 20 mkm and 1000 mkm. 12. A powder according to any of Claims 6 to 11 wherein the additive material consists of physiologically acceptable material. 13. A powder according to any of Claims 6 to 12 wherein the additive material includes one or more compounds selected from amino acids and derivatives thereof, and peptides and polypeptides having a molecular weight from 0.25 to 1000 kDa, and derivatives thereof. 14. A powder according to any of Claims 6 to 13, wherein the additive material includes one or more water soluble materials. 15. A powder according to Claim 14, wherein the additive material comprises a phospholipid or a derivative thereof. 16. A powder according to Claim 15, wherein the additive material comprises soya lecithin. 17. A powder according to any of Claims 6 to 16, wherein the additive material includes or consists of one or more surface active materials. 18. A powder according to any of Claims 6 to 17, wherein the additive material is an anti-adherent material. 19. A powder according to any of Claims 6 to 18, wherein the additive material is an anti-friction agent 20. A powder according to any of Claims 6 to 19, wherein the additive material includes dipolar ions. 21. A powder according to Claim 22 wherein the additive material consists of zwitterions. 22. A powder according to any of Claims 6 to 21 wherein the additive material is in the form of particles. 23. A powder according to Claim 22 wherein at least 95% by weight of the additive particles have a diameter less than 100 mkm. 24. A powder according to Claim 23 wherein the mass median diameter of the additive particles is not more than about 10 mkm. 25. A powder according to any of Claims 6 to 24 wherein the powder consists of not less than 0.1% by weight of additive particles based on the weight of the carrier particles. 26. A powder according to any of Claims 6 to 25 wherein the additive material forms a discontinuous covering on the surfaces of the carrier particles. 27. A powder according to any of Claims 6 to 29 wherein the mass median diameter of the active articles is not more than 10 mkm. 28. A powder according to any of Claims 6 to 27 wherein the active particles include a β2-agonist. 29. A powder according to Claim 28 wherein the active particles include salbutanol, a salt of salbutamol or a combination thereof. 30. A powder according to any of Claims 6 to 29 wherein the active particles include beclomethasone dipropionate. 31. Particle for use in a powder according to any of Claims 6 to 30, including carrier particles comprising one or more crystalline sugars of a diameter between 20 mkm and 1000 mkm and an additive material chosen from a group, consisting of amino acid and derivatives thereof, peptides, polypeptides and derivatives thereof, surface active materials., anti-adherent materials, anti-friction agents and additive material, wherein at least some of the additive material being attached to the surfaces of the carrier particles. 32. A method of producing particles according to Claim 31, the method including the step of mixing carrier particles of a size suitable for use in dry powder inhalers with additive material which becomes attached to the surfaces of the carrier particles. 33. A method according to Claim 32, wherein the method further includes the step of selecting from a sample of carrier particles an advantageous range of size of carrier particles prior to the mixing step. 34. A method according to Claim 36 or 33, wherein the additive material is in the form of particles when it is mixed with the carrier particles. 35. A method according to Claim 34, wherein the method further includes the step of selecting from a sample of additive particles an advantageous range of size of additive particles prior to the mixing step. 36. A method according to Claim 32, wherein additive material is added in the form of a liquid, a solution or a suspension. 37. A method according to any of Claims 32 to 36 wherein the additive material and the carrier particles are mixed for between 0. l hours and 0.5 hours. 38. A method according to any of Claims 32 to 37 wherein the carrier particles are mixed with the additive material using a tumbling blender. 39. A method according to any of Claims 32 to 38 wherein the method further includes the step of treating the carrier particles to dislodge small grains from the surfaces of the carrier particles, without substantially hanging the size of the carrier particles during the treatment. 40. A method according to Claim 32 wherein the mixing step is prior to the treatment step. 41. A method according to Claim 39 or Claim 40 wherein the small grains become reattached to the surfaces of the carrier particles. 42. A method according to any of Claims 39 wherein the treatment step is a milling step. 43. A method according to Claim 42 wherein the milling step is performed in a ball mill. 44. A method according to Claim 43 wherein the particles are milled using plastics balls. 45. A method according to any of Claims 42 to 44 wherein the particles are milled for between about 0.25 hours and 6 hours. 46. 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 dry powder inhalers with additive material such that the additive material becomes attached to the surfaces of the carrier particles. (b) treating the carrier particles to dislodge small grains from the surfaces of the carrier particles, without substantially changing the size of the carrier particles during the treatment and (c) mixing the treated particles with active particles such that active particles adhere to the surfaces of the carrier particles and/or the additive material. 47. Particles for use in a dry powder inhaler wherein the particles are made by a method according to any of Claims 32 to 45. 48. A powder for use in a dry powder inhaler wherein the powder is made by a method according to Claim.