Powder compositions for inhalation

Abstract

The present invention relates to pharmaceutical powders for inhalation produced by a method consisting of a first step of mixing particles of a force-controlling agent selected from a salt of a fatty acid with particles of one or more pharmacologically active materials and a second step of sieving or blending the powder with a carrier material.

What is claimed is: 
     
         1 . A pharmaceutical powder for inhalation produced by a method consisting of a first step (a) of mixing particles of a force-controlling agent selected from a salt of a fatty acid with particles of one or more pharmacologically active materials,
 wherein the mixing is achieved by one or more of the processes of sieving or blending, provided that the blending is not carried out in a high shear mixer,   wherein the mixing results in the particles of the force-controlling agent being disposed on the surface of the particles of the one or more pharmacologically active materials as either a particulate coating or as a continuous or discontinuous film; and a second step of   (b)(1) sieving or blending the powder obtained in step (a) with 50-99 weight percent of a carrier material based on the total weight of the formulation, or   (b)(2) blending the powder obtained in step (a) with a first portion of a carrier material to form a second mixture, and in a subsequent step mixing the remainder of the carrier material with said second mixture,   said carrier material having a particle size of 50-500 μm,   wherein the particles of one or more pharmacologically active materials comprise particles of a corticosteroid, a leukotriene antagonist, a phosphodiesterase inhibitor, a platelet activating factor inhibitor, a potassium channel opener, a pain killer, and a potency agent.   
     
     
         2 . The pharmaceutical powder of  claim 1 , wherein the second step is step (b)(2), blending the powder obtained in step (a) with a first portion of a carrier material to form a second mixture, and in a subsequent step mixing the remainder of the carrier material with said second mixture. 
     
     
         3 . The pharmaceutical powder of  claim 1  or  2 , wherein the blending is carried out in a diffusion blender, tumble blender, bin blender, or conical blender. 
     
     
         4 . The pharmaceutical powder of  claim 1 , wherein the force-controlling agent is present in amounts of up to 5.0% by weight based on the total weight of the formulation. 
     
     
         5 . The pharmaceutical powder of  claim 1 , wherein the force-controlling agent is present in amounts of 0.01 to 5.0% by weight based on the total weight of the formulation. 
     
     
         6 . The pharmaceutical powder of  claim 1 , wherein the carrier material is selected from glucose, lactose, lactose mono-hydrate, sucrose, trehalose, mannitol, xylitol, polylactic acid, or mixtures thereof. 
     
     
         7 . The pharmaceutical powder of  claim 6 , wherein the carrier material is lactose mono-hydrate. 
     
     
         8 . The pharmaceutical powder of  claim 1 , wherein the one or more pharmacologically active materials is selected from the group consisting of pharmacologically active materials having a contact angle against water that is less than 90°. 
     
     
         9 . The pharmaceutical powder of  claim 1 , wherein the one or more pharmacologically active materials is selected from the group consisting of pharmacologically active materials having an octanol-water partition coefficient (log P) smaller than 2. 
     
     
         10 . The pharmaceutical powder of  claim 1 , wherein the fatty acid is selected from the group consisting of lauric acid, palmitic acid, stearic acid, erucic acid, and behenic acid. 
     
     
         11 . The pharmaceutical powder of  claim 10 , wherein the salt of the fatty acid is magnesium stearate. 
     
     
         12 . The pharmaceutical powder of  claim 1 , wherein the corticosteroid is selected from the group consisting of butixocart, rofleponide, budesonide, ciclosenide, mometasone, fluticasone, beclomethasone, loteprednol or triamcinolone. 
     
     
         13 . The pharmaceutical powder of  claim 1 , wherein the leukotriene antagonist is selected from the group consisting of andolast, iralukast, pranlukast, imitrodast, seratrodast, zileuton, zafirlukast and montelukast. 
     
     
         14 . The pharmaceutical powder of  claim 1 , wherein the phosphodiesterase inhibitor is selected from the group consisting of filaminast and piclamilast. 
     
     
         15 . The pharmaceutical powder of  claim 1 , wherein the platelet activating factor inhibitor is selected from the group consisting of apafant and israpafant. 
     
     
         16 . The pharmaceutical powder of  claim 1 , wherein the potassium channel opener is selected from the group consisting of amiloride and furosemide. 
     
     
         17 . The pharmaceutical powder of  claim 1 , wherein, the pain killer is selected from the group consisting of morphine, fentanyl, pentazocine, buprenorphine, pethidine, tilidine, methadone and heroin. 
     
     
         18 . The pharmaceutical powder of  claim 1 , wherein the potency agent is selected from the group consisting of sildenafil, alprostadil and phentolamine. 
     
     
         19 . The pharmaceutical powder of  claim 1 , wherein the powder has a blend homogeneity with a relative standard deviation of drug content of less than 5%. 
     
     
         20 . The pharmaceutical powder of  claim 19 , wherein the powder has a blend homogeneity with a relative standard deviation of drug content of less than 3%. 
     
     
         21 . A dry powder inhaler device comprising the pharmaceutical powder of  claim 1 .