Pharmaceutical composition for modified release

Abstract

A pharmaceutical composition for modified release, comprising (1) (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide, or a pharmaceutically acceptable salt thereof, (2) at least one additive which ensures penetration of water into the pharmaceutical composition and which has a solubility such that the volume of water required for dissolving 1 g of the additive is 10 mL or less, and (3) a hydrogel-forming polymer having an average molecular weight of approximately 100,000 or more, or a viscosity of 12 mPa·s or more at a 5% aqueous solution at 25 C is disclosed.

1 - 15 . (canceled) 
     
     
         16 . A process of manufacturing a sustained release pharmaceutical composition, the process comprising mixing (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide, or a pharmaceutically acceptable salt thereof, with:
 at least one additive having a water solubility of at least 0.1 g/mL at 20±5° C.; and 
 a hydrogel-forming polymer having an average molecular weight of 100,000 to 8,000,000 or a viscosity of 12 mPa·s or more in a 5% aqueous solution at 25° C., 
 wherein an amount of the additive is 5% by weight to 75% by weight with respect to a total weight of the pharmaceutical composition, and an amount of the hydrogel-forming polymer is 1% by weight to 40% by weight with respect to the total weight of the pharmaceutical composition. 
 
     
     
         17 . The process according to  claim 16 , wherein the at least one additive is at least one compound selected from the group consisting of polyethylene glycol, polyvinylpyrrolidone, D-mannitol, D-sorbitol, xylitol, lactose, sucrose, anhydrous maltose, D-fructose, dextran, glucose, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan higher fatty acid ester, sodium chloride, magnesium chloride, citric acid, tartaric acid, glycine, β-alanine, lysine hydrochloride, and meglumine. 
     
     
         18 . The process according to  claim 16 , wherein the hydrogel-forming polymer is at least one compound selected from the group consisting of polyethylene oxide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, and a carboxyvinyl polymer. 
     
     
         19 . (canceled) 
     
     
         20 . The process according to  claim 16 , wherein the average molecular weight of the hydrogel-forming polymer is 100,000 to 2,000,000. 
     
     
         21 . The process according to  claim 16 , wherein the average molecular weight of the hydrogel-forming polymer is 100,000 to 5,000,000. 
     
     
         22 . The process according to  claim 16 , wherein the pharmaceutical composition comprises 10 mg to 200 mg of (R)-2-(2-aminothiazol-4-yl)-4′-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide. 
     
     
         23 . The process according to  claim 22 , wherein the pharmaceutical composition is a tablet. 
     
     
         24 . The process according to  claim 16 , wherein the pharmaceutical composition is a tablet. 
     
     
         25 . The process according to  claim 16 , wherein a drug dissolution rate from the pharmaceutical composition is 39% or less after 1.5 hours, and at least 75% after 7 hours, as measured in accordance with United States Pharmacopoeia in 900 mL of a USP buffer having a pH of 6.8 at a paddle rotation speed of 200 rpm. 
     
     
         26 . The process according to  claim 25 , wherein the drug dissolution rate from the pharmaceutical composition is at least 92% after 4.5 hours.