Formulations for use in inhaler devices

Abstract

A formulation for an inhaler device comprises carrier particles having a diameter of at least 50 μm and a mass median diameter of at least 175 μm; active particles; and additive material to which is able to promote release of the active particles from the carrier particles on actuation of the inhaler device. The formulation has excellent flowability even at relatively high fine particle contents.

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; active patents and additive material which is able to promote release of the active particles from the carrier particles on actuation of the inhaler device, the formulation comprising more than 5% by weight, based on the total weight of the formulation, of particles of aerodynamic diameter less than 20 μm, and the formulation having a flowability index of 12 mm or less. 
     
     
         2 . A formulation according to  claim 1 , in which the mass median diameter of the carrier particles is at least 200 μm. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . A formulation according to  claim 1 , in which the carrier particles are of lactose. 
     
     
         6 . A formulation according to  claim 1 , in which the carrier particles are of a material having a fissured surface. 
     
     
         7 . 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 . 
     
     
         8 . (canceled) 
     
     
         9 . 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 . 
     
     
         10 . 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. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . A formulation according to  claim 1 , in which the additive material is present in an amount of not more than 10% by weight based on the total weight of the formulation. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A formulation according to  claim 1 , in which the additive material comprises one or more compounds selected from the group consisting of magnesium stearate, calcium stearate, sodium stearate, stearate, stearic acid, stearylamine, sodium stearyl fumarate, oleic acid, starch, behenic acid, glyceryl behenate and sodium benzoate. 
     
     
         22 . A formulation according to  claim 21 , in which the additive is magnesium stearate. 
     
     
         23 . (canceled) 
     
     
         24 . A formulation according to  claim 1 , in which the additive material is in particulate form. 
     
     
         25 . A formulation according to  claim 24 , in which at least 90% by weight of the additive particles have an aerodynamic diameter of less than 100 μm. 
     
     
         26 . A formulation according to  claim 24 , in which the mass median aerodynamic diameter of the additive particles is not more than about 100 μm. 
     
     
         27 . A formulation according to  claim 1 , which comprises not less than 0.01% by weight of additive material based on the weight of the formulation. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A formulation according to  claim 1 , which contains up to 50% by weight of active particles, based on the total weight of active particles, additive material and carrier particles. 
     
     
         32 . (canceled) 
     
     
         33 . A formulation according to  claim 1 , which comprises at least 50% by weight carrier particles, based on the total weight of the formulation. 
     
     
         34 . (canceled) 
     
     
         35 . A formulation according to  claim 1 , in which the active particles comprise a therapeutically active agent for the prevention or treatment of respiratory disease. 
     
     
         36 . (canceled) 
     
     
         37 . A formulation according to  claim 35 , in which active particles comprise a therapeutically active agent having systemic activity. 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . A formulation according to  claim 1 , which further comprises fine particles of an excipient material of aerodynamic diameter not more than 50 μm. 
     
     
         41 . A formulation according to  claim 40 , in which the mass median aerodynamic diameter of the fine excipient particles is not more than 15 μm. 
     
     
         42 . (canceled) 
     
     
         43 . A formulation according to  claim 40 , which includes the fine excipient particles in an amount of not less than 4% by weight, based on the total weight of the formulation. 
     
     
         44 . A formulation according to  claim 40 , including fine excipient particles in an amount of up to 20% by weight, based on the total weight of the formulation. 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . A formulation according to  claim 40 , comprising up to 20% by weight fine excipient particles and up to 10% by weight additive material, based on the total weight of the formulation. 
     
     
         50 . A formulation according to  claim 1 , which comprises up to 10% by weight additive material, based on the total weight of the formulation. 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . 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 90% by weight of a therapeutically active agent;   from 0.01 to 50% by weight of an additive material which is able to promote released of the active material on actuation of the inhaler device;   in each case, by weight, based on the total weight of the carrier particles, active agent and additive material.   
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . (canceled) 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . An inhaler device comprising a formulation according to  claim 1 . 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . A method of manufacturing a formulation according to  claim 1 , comprising mixing the additive material with the carrier particles and the active particles. 
     
     
         64 . A method according to  claim 63 , in which the additive material is mixed with fine excipient material before mixing with the carrier particles and the active particles. 
     
     
         65 . A method of increasing the fine particle fraction obtainable from a formulation for an inhaler device comprising combining fissured carrier particles of mass median diameter of at least 175 μm with an additive material. 
     
     
         66 . A formulation according to  claim 1 , comprising composite particles comprising additive material and fine excipient material consisting of one or more crystalline sugars, prepared as a pre-blend by milling or high-energy mixing the additive and fine excipient material prior to the addition of the active and carrier particles; wherein the additive material includes one or more compounds selected from amino acids and derivatives thereof; peptides and polypeptides having a molecular weight from 0.25 to 1000 Kda, and derivatives thereof; phospholipids or a derivative thereof; fatty acids and derivatives thereof; or a surface active material. 
     
     
         67 . A formulation according to  claim 1 , wherein said carrier particles have no tendency to disintegrate on expulsion from the inhaler device. 
     
     
         68 . A method according to  claim 63 , comprising forming composite particles comprising additive material and fine excipient material consisting of one or more crystalline sugars, prepared as a pre-blend by milling or high-energy mixing the additive and fine excipient material prior to the addition of the active and carrier particles; wherein the additive material includes one or more compounds selected from amino acids and derivatives thereof; peptides and polypeptides having a molecular weight from 0.25 to 1000 Kda, and derivatives thereof; phospholipids or a derivative thereof; fatty acids and derivatives thereof; or a surface active material.