Formulations for use in inhaler devices

1. A formulation for use in an inhaler device, comprising

carrier particles in the form of an agglomerate consisting of a plurality of crystals fused to one another, wherein the carrier particles have a diameter of at least 50 μm and a mass median aerodynamic diameter of at least 175 μm and a fissured surface in which the fissures between the crystals of the agglomerate are at least 20 μm wide and at least 20 μm deep;

fine particles consisting of an excipient material consisting of one or more crystalline sugars and having a mass median aerodynamic diameter of not more than 20 μm; and

active particles; wherein the fine excipient particles are present in an amount of from not less than 5% by weight based on the total weight of the formulation, to 50% by weight based on the total weight of the carrier particles, fine excipient particles and active particles.

2. A formulation according to claim 1 , in which the mass median diameter of the carrier particles is at least 200 μm.

3. A formulation according to claim 1 , in which the mass median aerodynamic diameter of the fine excipient particles is not more than 15 μm.

4. A formulation according to claim 3 , in which the mass median aerodynamic diameter of the fine excipient particles is not more than 10 μm.

5. A formulation according to claim 1 , in which the carrier particles and the fine excipient particles are of the same material.

6. A formulation according to claim 1 , in which at least the carrier particles are of a crystalline sugar.

7. A formulation according to claim 6 , in which the carrier particles are of dextrose or lactose.

8. A formulation according to claim 7 , in which the carrier particles are of lactose.

9. A formulation according to claim 1 , in which the fine excipient particles are of dextrose or lactose.

10. A formulation according to claim 9 , in which the fine excipient particles are of lactose.

11. A formulation according to claim 1 , in which the carrier particles are of a crystalline sugar having a tapped density not exceeding 0.75 g/cm 3 .

12. A formulation according to claim 1 , in which the carrier particles have a tapped density not exceeding 0.70 g/cm 3 .

13. A formulation according to claim 1 , in which the carrier particles have a bulk density as measured by mercury intrusion porosimetry of not exceeding 0.6 g/cm3.

14. A formulation according to claim 1 , in which the carrier particles are obtainable by a wet granulation process.

15. A formulation according to claim 1 , in which the carrier particles are dendritic spherulites.

16. A formulation according to claim 1 , which contains up to 90% by weight of active particles and fine excipient particles, based on the total weight of active particles, fine excipient particles and carrier particles.

17. A formulation according to claim 16 , which contains up to 50% by weight of active particles and fine excipient particles, based on the total weight of active particles, fine excipient particles and carrier particles.

18. A formulation according to claim 17 , which contains up to 20% by weight of active particles and fine excipient particles, based on the total weight of active particles, fine excipient particles and carrier particles.

19. A formulation according to claim 1 , in which the active particles are present in an amount of from 0.01 to 90% by weight, based on the total weight of active particles and fine excipient particles.

20. A formulation according to claim 19 , in which the active particles are present in an amount of from 0.1 to 50% by weight, based on the total weight of active particles and fine excipient particles.

21. A formulation according to claim 1 , which contains up to 20% by weight of active particles, based on the total weight of the formulation.

22. A formulation according to claim 1 , which comprises at least 50% by weight carrier particles, based on the total weight of the formulation.

23. A formulation according to claim 22 , which comprises at least 70% by weight carrier particles, based on the total weight of the formulation.

24. A formulation according to claim 1 , wherein the fine excipient particles are present in an amount of from not less than 5% by weight based on the total weight of the formulation up to 20% by weight based on the total weight of the formulation.

25. A formulation according to claim 24 , in which the fine excipient particles are present in an amount of from not less than 5% by weight based on the total weight of the formulation up to 15% by weight based on the total weight of the formulation.

26. A formulation according to claim 1 , which contains at least 20% by weight, based on the total weight of the formulation, of particles of diameter less than 20 μm.

27. A formulation according to claim 1 , in which the active particles comprise an agent having therapeutic activity when delivered into the lung.

28. A formulation according to claim 27 , in which the active particles comprise a therapeutically active agent for the prevention or treatment of respiratory disease.

29. A formulation according to claim 1 , in which the active particles comprise one or more active agents selected from β2-agonists, ipratropium bromide, steroids, cromones and leukotriene receptor antagonists.

30. A formulation according to claim 27 , in which the active particles comprise a therapeutically active agent for systemic use.

31. A formulation according to claim 27 , in which the active particles comprise one or more agents selected from peptides, polypeptides, proteins and DNA fragments.

32. A formulation according to claim 31 , in which the active particles comprise insulin.

33. A formulation according to claim 1 , comprising more than 5% by weight, based on the total weight of the formulation, of particles of aerodynamic diameter less than 20 μm, the formulation having a flowability index of 12 mm or less.

34. A formulation according to claim 33 , which comprises more than 10% by weight particles of aerodynamic diameter less than 20 μm.

35. A formulation according to claim 1 , comprising:

from 5 to 90% by weight carrier particles having a diameter of at least 50 μm and a mass median diameter of at least 175 μm;

from 0.01 to 80% by weight of a therapeutically active agent;

from 9 to 50% by weight of particles of fine excipient material;

in each case, by weight, based on the total weight of the carrier particles, active agent and fine excipient material.

36. An inhaler device comprising a formulation according to claim 1 .

37. A device according to claim 36 , which is a dry powder inhaler.

38. A device according to claim 37 , which is a pressurised metered dose inhaler.

39. A method of manufacturing a formulation according to claim 1 , comprising mixing the fine excipient particles with the carrier particles and the active particles.

40. The formulation of claim 1 which has a flowability index of 12 mm or less.

41. The formulation of claim 1 , wherein each carrier particle contains at least three lactose primary crystals of the tomahawk shape.

42. A formulation as claimed in claim 1 , wherein the crystals of the agglomerate are fused to one another by solid bridges.