Drug microparticles

Abstract

Provided are microparticles of active pharmaceutical ingredients, drug delivery vehicles comprising same, and methods for making them.

What is claimed is;  
     
         1 . A drug delivery vehicle comprising a pharmaceutical carrier particle bearing microparticles of a drug deposited on the pharmaceutical carrier particle from a solid solution of the drug in a sublimable carrier.  
     
     
         2 . The drug delivery vehicle of  claim 1  wherein the drug is a poorly water soluble drug.  
     
     
         3 . The drug delivery vehicle of  claim 2  wherein the poorly water soluble drug is selected from the group consisting of: fenofibrate, itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.  
     
     
         4 . The drug delivery vehicle of  claim 1  wherein the sublimable carrier comprises one or more members selected from the group consisting of menthol, thymol, camphor, t-butanol, trichloro-t-butanol, imidazole, coumarin, acetic acid (glacial), dimethylsulfone, urea, vanillin, camphene, salicylamide, and 2-aminopyridine.  
     
     
         5 . The drug delivery vehicle of  claim 4  wherein the sublimable carrier is menthol.  
     
     
         6 . The drug delivery vehicle of  claim 1  wherein the pharmaceuticle carrier particle comprises at least on pharmaceutical particle selected from starch particles, microcrystalline starch particles, microcrystalline cellulose particles, lactose particles, and sugar particles.  
     
     
         7 . The drug delivery vehilcle of  claim 6  wherein the pharmaceutical carrier particle comprises particles of microcrystalline cellulose.  
     
     
         8 . The method of  claim 6  wherein the solid solution is formed by combining the drug and sublimable carrier with an organic solvent and thereafter evaporating the organic solvent to obtain the solid solution.  
     
     
         9 . A method of making a drug delivery vehicle comprising the steps of: 
 a) forming a solid solution of the drug and a sublimable carrier on the surface of a pharmaceutical carrier particle, and    b) subliming the sublimable carrier from the solid solution to deposit microparticles of the drug on the surface of the pharmaceutical carrier particle to obtain the drug delivery vehicle.    
     
     
         10 . The method of  claim 9  wherein the solid solution is formed by combining the drug with molten sublimable carrier, applying the combination to at least one pharmaceutical carrier particle, and thereafter allowing the combination to solidify to obtain the solid solution on the surface of the pharmaceutical carrier particle.  
     
     
         11 . The method of  claim 9  wherein the solid solution is formed by combining the drug and the sublimable carrier with an organic solvent, applying the combination to at least one pharmaceutical carrier particle, and evaporating the organic solvent to obtain the solid solution on the surface of the at least one pharmaceutical carrier particle.  
     
     
         12 . The method of  claim 11  wherein the solvent is ethanol.  
     
     
         13 . The method of  claim 9  wherein the drug is selected from the group consisting of fenofibrate, itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.  
     
     
         14 . The method of  claim 9  wherein the sublimable carrier is selected from the group consisting of menthol, thymol, camphor, t-butanol, trichloro-t-butanol, imidazole, coumarin, acetic acid (glacial), dimethylsulfone, urea, vanillin, camphene, salicylamide, and 2-aminopyridine.  
     
     
         15 . The method of  claim 9  wherein the pharmaceutical carrier particle is selected from the group consisting of starch particles, sugar particles, lactose particles, particles of microcrystalline cellulose, and mixtures of any of these.  
     
     
         16 . The method of  claim 9  wherein the sublimable carrier is sublimed from the solid solution by treating the pharmaceitical carrier particles in a fludized bed drier at a temperature below the melting point of the solid solution.  
     
     
         17 . A pharmaceutical composition comprising a plurality of microparticles of a drug and at least one pharmaceutically acceptable excipient, wherein the microparticles are formed by removing sublimable carrier from a solid solution of the drug in the sublimable carrier.  
     
     
         18 . The pharmaceutical composition of  claim 17  wherein the solid solution is formed on the surface of a plurality of pharmaceutical carrier particle.  
     
     
         19 . The pharmaceutical composition of  claim 17  wherein the sublimable carrier is removed from the solid solution that is on the surfaces of the plurality of pharmaceutical carrier particles, whereby the plurality of microparticles are born by the plurality of pharmaceutical carrier particles.  
     
     
         20 . An oral solid dosage form comprising a pharmaceutical composition according to  claim 16.