Pharmaceutical formulation comprising an aqueous suspension of an androstane derivative for the treatment of inflammatory and allergic conditions

Abstract

There is provided a pharmaceutical formulation comprising an aqueous suspension of particulate compound of formula (I) or a solvate thereof.

1 - 4 . (canceled)  
     
     
         5 . A pharmaceutical formulation comprising 
 a pharmaceutical formulation which comprises:    an aqueous suspension of particulate compound of formula (I)                          or a solvate thereof, and one or more preservatives, wherein the preservative comprises disodium edatate.    
     
     
         6 - 8 . (canceled)  
     
     
         9 . A pharmaceutical formulation according to  claim 5  which further comprises one or more wetting agents.  
     
     
         10 . A pharmaceutical formulation according to  claim 9  wherein the wetting agent comprises polyoxyethylene (20) sorbitan monooleate.  
     
     
         11 . A pharmaceutical formulation according to  claim 9  wherein the wetting agent is present within the formulation in an amount of between 0.001 and 0.05% (w/w), based on the total weight of the formulation.  
     
     
         12 . A pharmaceutical formulation according to  claim 5  which further comprises: 
 one or more isotonicity adjusting agents.    
     
     
         13 . A pharmaceutical formulation according to  claim 12  wherein the isotonicity adjusting agent comprises dextrose.  
     
     
         14 . A pharmaceutical formulation according to  claim 12  wherein the isotonicity adjusting agent is present within the formulation in an amount of between 0.1 and 10% (w/w), based on the total weight of the formulation.  
     
     
         15 . A pharmaceutical formulation according to  claim 12  characterised in that it is isotonic with fluids of the nasal cavity.  
     
     
         16 . A pharmaceutical formulation according to  claim 12  which is pH adjusted to between 5 and 7.  
     
     
         17 . A pharmaceutical formulation according to  claim 16  which is pH adjusted using hydrochloric acid and/or sodium hydroxide  
     
     
         18 . A pharmaceutical formulation according to  claim 5  wherein the compound of formula (I) or solvate thereof is present within the formulation in an amount between 0.005% and 1% (w/w), based on the total weight of the formulation.  
     
     
         19 . A pharmaceutical formulation according to  claim 5  wherein the particles of the compound of formula (I) have a mass mean diameter of between 0.5 and 10 μm.  
     
     
         20 . A pharmaceutical formulation according to  claim 19  wherein the particles of the compound of formula (I) have a mass mean diameter of between 1 and 5 μm.  
     
     
         21 . A pharmaceutical formulation according to  claim 5  wherein the compound of formula (I) is in the form of unsolvated Form 1 polymorph.  
     
     
         22 . A pharmaceutical formulation which comprises: 
 an aqueous suspension of particulate compound of formula (I)                          or a solvate thereof wherein the particle size of the compound of formula (I) has been reduced.    
     
     
         23 . A pharmaceutical composition as claimed in  claim 22  wherein the particle size has been reduced by micronisation.  
     
     
         24 . A pharmaceutical composition as claimed in  claim 22  wherein the particle size has been reduced by microfluidisation.  
     
     
         25 . A pharmaceutical formulation as claimed in  claim 22 , wherein the compound of formula (I) was substantially in the form of equant or substantially equant particles, prior to particle size reduction.  
     
     
         26 . A pharmaceutical formulation as claimed in  claim 22  wherein the compound of formula (I) was substantially in the form of tetragonal bipyramidal or substantially tetragonal bipyramidal particles prior to particle size reduction.  
     
     
         27 . A pharmaceutical formulation as claimed in  claim 23  wherein the compound of formula (I) is substantially in the form of acicular particles.  
     
     
         28 . A pharmaceutical formulation according to  claim 22  which comprises 
 (i) one or more suspending agents;    (ii) one or more preservatives;    (iii) one or more wetting agents; and    (iv) one or more isotonicity adjusting agents    
     
     
         29 . A pharmaceutical formulation according to  claim 28  wherein the suspending agent is microcrystalline cellulose and carboxy methylcellulose sodium, the preservative is EDTA and benzalkonium chloride, the wetting agent is polyoxyethylene (20) sorbitan monooleate and the isotonicity adjusting agent is dextrose.  
     
     
         30 . A pharmaceutical formulation according to  claim 22  which comprises another therapeutically active agent.  
     
     
         31 . A pharmaceutical formulation according to  claim 30 , wherein the other therapeutically active agent is an anti-histamine or an anti-allergic.  
     
     
         32 . A container comprising a pharmaceutical formulation which comprises: an aqueous suspension of particulate compound of formula (I)  
       
         
           
           
               
               
           
         
         or a solvate thereof wherein the particle size of the compound of formula (I) has been reduced.  
       
     
     
         33 . A device adapted for intranasal delivery of a pharmaceutical formulation comprising a container according to  claim 32 .  
     
     
         34 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       substantially in the form of equant or substantially equant particles.  
     
     
         35 . A compound as claimed in  claim 34  wherein the particles are in the form of tetragonal bipyramidal or substantially tetragonal bipyramidal particles.  
     
     
         36 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       substantially in the form of acicular particles.  
     
     
         37 . A method of treatment of allergic rhinitis which comprises administering to a patient a pharmaceutically acceptable amount of a formulation according to  claim 22 .  
     
     
         38 . The method according to  claim 37  wherein the administration is once-per-day.  
     
     
         39 . A pharmaceutical formulation as claimed in  claim 22  for use in human or veterinary medicine in the treatment of patients with an inflammatory and/or an allergic condition.  
     
     
         40 . A pharmaceutical formulation as claimed in  claim 39  for use in treatment once-per-day.  
     
     
         41 . A process for the manufacture of a medicament for the treatment of patients with an inflammatory and/or allergic condition comprising preparing a pharmaceutical formulation according to  claim 22 .  
     
     
         42 . (canceled)  
     
     
         43 . A process for the preparation of a compound of formula (I) substantially in the form of equant or substantially equant particles which process comprises dissolving a compound of formula (I) in a suitable solvating solvent and crystallising the compound.  
     
     
         44 . A process as claimed in  claim 43  wherein the solvating solvent is acetone, propan-2-ol, ethylacetate or tetrahydrofuran.  
     
     
         45 . A process as claimed in  claim 44  wherein the solvating agent is acetone pr propan-2-ol.  
     
     
         46 . A process as claimed in  claim 43  wherein the compound of formula (I) is substantially in the form of tetragonal bipyramidal particles.