Method for Preparing a Granulate Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients

Abstract

A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

1 - 36 . (canceled) 
     
     
         37 . A method for preparing a granulation comprising 5-methyl-1-phenyl-2-(1H)-pyridone and pharmaceutically acceptable excipients, the method comprising the steps of preparing the granulation using a type and an amount of an excipient selected to increase the AUC of the 5-methyl-1-phenyl-2-(1H)-pyridone upon oral administration, as compared to 5-methyl-1-phenyl-2-(1H)-pyridone without excipients orally administered in a capsule shell. 
     
     
         38 . The method of  claim 37  wherein the method comprises the steps of preparing the granulation using a type and an amount of binder selected to increase the AUC of the 5-methyl-1-phenyl-2-(1H)-pyridone upon oral administration, as compared to 5-methyl-1-phenyl-2-(1H)-pyridone without excipients orally administered in a capsule shell. 
     
     
         39 . The method of  claim 38 , wherein the binder is a binder that interacts with the amide carbonyl group of the 5-methyl-1-phenyl-2-(1H)-pyridone. 
     
     
         40 . The method of  claim 37 , wherein the pharmaceutically acceptable excipients comprise one or more of a disintegrator, a binder, a filler, and a lubricant. 
     
     
         41 . The method of  claim 40 , wherein said disintegrator comprises one or more of agar-agar, algins, calcium carbonate, carboxmethylcellulose, cellulose, clays, colloid silicon dioxide, croscarmellose sodium, crospovidone, gums, magnesium aluminium silicate, methylcellulose, polacrilin potassium, sodium alginate, low substituted hydroxypropylcellulose, and cross-linked polyvinylpyrrolidone hydroxypropylcellulose, sodium starch glycolate, and starch. 
     
     
         42 . The method of  claim 40 , wherein the binder comprises one or more of microcrystalline cellulose, hydroxymethyl cellulose, hydroxypropylcellulose, and polyvinylprryolidone. 
     
     
         43 . The method of  claim 40 , wherein said filler comprises one or more of calcium carbonate, calcium phosphate, dibasic calcium phosphate, tribasic calcium sulfate, calcium carboxymethylcellulose, cellulose, dextrates, dextrin, dextrose, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltodextrins, maltose, sorbitol, starch, sucrose, sugar, and xylitol. 
     
     
         44 . The method of  claim 40 , wherein said lubricant comprises one or more of agar, calcium stearate, ethyl oleate, ethyl laureate, glycerin, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium oxide, magnesium stearate, mannitol, poloxamer, glycols, sodium benzoate, sodium lauryl sulfate, sodium stearyl, sorbitol, stearic acid, talc, and zinc stearate. 
     
     
         45 . The method of  claim 40 , wherein by weight of the granulation, said disintegrator is 2-10%, said binder is 2-30%, said filler is 2-30%, and said lubricant is 0.3-0.8%. 
     
     
         46 . The method of  claim 40 , wherein the excipients comprise magnesium stearate as a lubricant, microcrystalline cellulose as a binder, and croscarmellose sodium as a disintegrator. 
     
     
         47 . The method of  claim 37 , wherein, by weight of the granulation, the 5-methyl-1-phenyl-2-(1H)-pyridone comprises 70-95% and the pharmaceutically acceptable excipients comprise 5-30%. 
     
     
         48 . The method of  claim 37 , wherein the granulation comprises 100-400 mg 5-methyl-1-phenyl-2-(1H)-pyridone. 
     
     
         49 . The method of  claim 37 , wherein the granulation comprises a wet-granulated mixture.