Formulations for use in inhaler devices

Abstract

A formulation for use in an inhaler device comprises carrier particles having a diameter of at least 50 μm and a mass median diameter of at least 175 μm; fine particles of an excipient material having a mass median aerodynamic diameter of not more than 20 μm; and active particles. The formulation has excellent flowability even at relatively high contents of fine particles.

1 . A formulation for use in an inhaler device, comprising carrier particles having a diameter of at least 50 μm and a mass median diameter of at least 175 μm; fine particles of an excipient material having a mass median aerodynamic diameter of not more than 20 μm; 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 material having a fissured surface. 
     
     
         12 . A formulation according to  claim 11 , in which the carrier particles are of a crystalline sugar having a tapped density not exceeding 0.75 g/cm 3 . 
     
     
         13 . A formulation according to  claim 12 , in which the carrier particles have a tapped density not exceeding 0.70 g/cm 3 . 
     
     
         14 . 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/cm 3 . 
     
     
         15 . A formulation according to  claim 1 , in which the carrier particles are in the form of an agglomerate consisting of a plurality of crystals fused to one another. 
     
     
         16 . A formulation according to  claim 1 , in which the carrier particles are obtainable by a wet granulation process. 
     
     
         17 . A formulation according to  claim 1 , in which the carrier particles are dendritic spherulites. 
     
     
         18 . A formulation according  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. 
     
     
         19 . A formulation according to  claim 18 , 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. 
     
     
         20 . A formulation according to  claim 19 , 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. 
     
     
         21 . 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. 
     
     
         22 . A formulation according to  claim 21 , 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. 
     
     
         23 . A formulation according to  claim 1 , which contains up to 20% by weight of active particles, based on the total weight of the formulation. 
     
     
         24 . A formulation according  claim 1 , which comprises at least 50% by weight carrier particles, based on the total weight of the formulation. 
     
     
         25 . A formulation according to  claim 24 , which comprises at least 70% by weight carrier particles, based on the total weight of the formulation. 
     
     
         26 . A formulation according to  claim 1 , which contains at least 4% by weight fine excipient particles, based on the total weight of the formulation. 
     
     
         27 . A formulation according to  claim 1 , which contains up to 20% by weight fine excipient, based on the total weight of the formulation. 
     
     
         28 . A formulation according to  claim 27 , in which the fine excipient particles are present in an amount of up to 15% by weight based on the total weight of the formulation. 
     
     
         29 . 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. 
     
     
         30 . A formulation according to  claim 1 , in which the active particles comprise an agent having therapeutic activity when delivered into the lung. 
     
     
         31 . A formulation according to  claim 30 , in which the active particles comprise a therapeutically active agent for the prevention or treatment of respiratory disease. 
     
     
         32 . A formulation according to  claim 1 , in which the active particles comprise one or more active agents selected from .beta 2 -agonists, ipatropium bromide, steroids, cromones and leukotriene receptor antagonists. 
     
     
         33 . A formulation according to  claim 30 , in which the active particles comprise a therapeutically active agent for systemic use. 
     
     
         34 . A formulation according to  claim 1 , in which the active particles comprise one or more agents selected from peptides, polypeptides, proteins and DNA fragments. 
     
     
         35 . A formulation according to  claim 34 , in which the active particles comprise insulin. 
     
     
         36 . A formulation for use in a dry powder inhaler, 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. 
     
     
         37 . A formulation according to  claim 36 , which comprises more than 10% by weight particles of aero-dynamic diameter less than 20 μm. 
     
     
         38 . A formulation for use in an inhaler device, 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 of diameter less than 50 μm; in each case, by weight, based on the total weight of the carrier particles, active agent and fine excipient material. 
     
     
         39 - 40 . (canceled) 
     
     
         41 . An inhaler device comprising a formulation according to  claim 1 . 
     
     
         42 . A device according to  claim 41 , which is a dry powder inhaler. 
     
     
         43 . A device according to  claim 42 , which is a pressurised metered dose inhaler. 
     
     
         44 . A method of manufacturing a formulation according to any one of  claims 1  to  43 , comprising mixing the fine excipient particles with the carrier particles and the active particles.