Dry powder formulations

Abstract

A dry powder suitable for inhalation in a dry powder inhaler, the powder comprising a carrier, an active agent and at least 0.5% by weight of magnesium stearate, the powder being further characterized in that the less than 10% of the surface of the carrier material is covered with particles of magnesium stearate . The invention is also directed to a method of making dry powders by blending together the ingredients mentioned in a diffusion blender for a period time that is less than 60 minutes.

1 . A dry powder formulation for inhalation, comprising active particles and carrier particles for supporting the active particles, the formulation-further comprising magnesium stearate in an amount of at least 0.5% by weight of the formulation, wherein particles of magnesium stearate are disposed on the surface of the carrier particles to provide a surface coverage of less than 10% on the carrier particles.  
   
   
       2 . The dry powder formulation according to  claim 1 , wherein the surface coverage of carrier particles is from 1 to 5%.  
   
   
       3 . The dry powder formulation according to  claim 1 , wherein the magnesium stearate is present in amounts of 0.5 to 2% by weight.  
   
   
       4 . The dry powder formulation according to  claim 1 , wherein the magnesium stearate is present in amounts of form 0.6 to 1% by weight.  
   
   
       5 . The dry powder formulation according to  claim 1 , wherein the active particles comprise an active substance selected from the group consisting of beta-mimetics, anticholinergics, corticosteroids, leukotrienantagonists, phosphodiesterase inhibitors, PAF-inhibitors, potassium channel openers, analgesics, potency agents, macromolecules, pharmaceutically acceptable salts thereof and mixtures thereof.  
   
   
       6 . The dry powder formulation according to  claim 1 , wherein the carrier particles comprise a carrier material selected from monosaccharides, disaccharides, sugar alcohols, polylactic acid, or mixtures thereof.  
   
   
       7 . The dry powder formulation according to  claim 6 , wherein the carrier is lactose mono-hydrate.  
   
   
       8 . A method of making the dry powder formulation for inhalation according to  claim 1 , comprising the step of blending magnesium stearate with a carrier material in a diffusion blender for a period of less than 30 minutes to form a mixture.  
   
   
       9 . The method according to  claim 8 , further comprising the step of: 
 blending the mixture of magnesium stearate and carrier material with an active substance in a diffusion blender for a period of less than 30 minutes.    
   
   
       10 . A multi-dose dry powder inhaler containing the formulation according to  claim 1 .  
   
   
       11 . A method of making a dry powder consisting essentially of the consecutive steps of: 
 (i) admixing magnesium stearate with a carrier material in a diffusion blender for a period of less than 30 minutes; and    (ii) blending the mixture of step (i) with an active substance in a diffusion blender for a period of less than 30 minutes.    
   
   
       12 . The dry powder formulation according to  claim 5 , wherein the beta-mimetic is selected from the group consisting of Levalbuterol, Terbutalin, Reproterol, Salbutamol, Salmeterol, Formoterol, Fenoterol, Clenbuterol, Bambuterol, Tulobuterol, Broxaterol, Epinephrin, Isoprenaline and Hexoprenaline.  
   
   
       13 . The dry powder formulation according to  claim 5 , wherein the anticholinergic is selected from the group consisting of Tiotropium, Ipratropium, Oxitropium and Glycopyrronium.  
   
   
       14 . The dry powder formulation according to  claim 5 , wherein the corticosteroid is selected from the group consisting of Butixocart, Rofleponide, Budesonide, Ciclosenide, Mometasone, Fluticasone, Beclomethasone, Loteprednol and Triamcinolone.  
   
   
       15 . The dry powder formulation according to  claim 5 , wherein the leukotrienantagonist is selected from the group consisting of Andolast, Iralukast, Pranlukast, Imitrodast, Seratrodast, Zileuton, Zafirlukast and Montelukast.  
   
   
       16 . The dry powder formulation according to  claim 5 , wherein the phosphodiesterase-inhibitor is selected from Filaminast or Piclamilast.  
   
   
       17 . The dry powder formulation according to  claim 5 , wherein the PAF-inhibitor is selected from the group consisting of Apafant, Forapafant and Israpafant.  
   
   
       18 . The dry powder formulation according to  claim 5 , wherein the potassium channel opener is selected from Amiloride or Furosemide.  
   
   
       19 . The dry powder formulation according to  claim 5 , wherein the analgesic is selected from the group consisting of Morphine, Fentanyl, Pentazocine, Buprenorphine, Pethidine, Tilidine, Methadone and Heroin.  
   
   
       20 . The dry powder formulation according to  claim 5 , wherein the potency agent is selected from the group consisting of Sildenafil, Alprostadil and Phentolamine.  
   
   
       21 . The dry powder formulation according to  claim 5 , wherein the macromolecule is selected from the group consisting of proteins, peptides, oligopeptides, polypeptides, polyamino acids, nucleic acids, polynucleotides, oligo-nucleotides and high molecular weight polysaccharides.  
   
   
       22 . The dry powder formulation according to  claim 6 , wherein the monosaccharide or disaccharide is selected from the group consisting of glucose, lactose, lactose monohydrate, sucrose, trehalose and mixtures thereof.  
   
   
       23 . The dry powder formulation according to  claim 6 , wherein the sugar alcohol is selected from mannitol, xylitol, or a mixture thereof.