Process for producing spherical base granule comprising easily water-soluble drug

Abstract

Provided is a process for producing spherical base granules comprising a easily water-soluble drug and suited for film coating by spraying a layering liquid over pharmaceutically inert spherical core particles, thereby coating the particles with a layer comprising the easily water-soluble drug, wherein (1) the spherical core particles have a microcrystalline cellulose content of 30 mass % or greater and a water absorbing capacity of 0.5 cm 3 /g or greater; and (2) the layering liquid is an aqueous solution comprising at least the easily water-soluble drug and a low water-soluble saccharide.

The invention claimed is: 
     
       1. A process for producing spherical base granules comprising an easily water-soluble drug, which comprises spraying a layering liquid over pharmaceutically inert spherical core particles to thereby coat the particles with a drug-containing layer, wherein:
 (1) the spherical core particles have a microcrystalline cellulose content of 30 mass % or greater, a water absorbing capacity of 0.5 cm 3 /g or greater and a bulk density of about 0.5 to about 2.0 g/cm 3 ; 
 (2) the layering liquid is an aqueous solution comprising at least from 5 to 30 mass % of the easily water-soluble drug and from 1 to 30 mass % of D-mannitol; 
 (3) the easily water-soluble drug has a solubility of 1.5 g or greater in 1 cm 3  of water at 20° C.; and 
 (4)(3) the easily water-soluble drug is at least one selected from the group consisting of ethyl L-cysteine hydrochloride, cloperastine hydrochloride, procainamide hydrochloride, ceftizoxime sodium, migrenin, and loxoprofen sodium. 
 
     
     
       2. The process for producing spherical base granules comprising an easily water-soluble drug according to  claim 1 , wherein the coating rate of the drug-containing layer is 0.8 g/min or greater per kg of the spherical core particles. 
     
     
       3. The process for producing spherical base granules comprising an easily water-soluble drug according to any one of  claims 1  or  2 , wherein the spherical core particles comprise microcrystalline cellulose in an amount of 70 mass % or greater. 
     
     
       4. The process for producing spherical base granules comprising an easily water-soluble drug according to  claim 1  or  2 , wherein the water absorbing capacity of the spherical core particles is 0.7 cm 3 /g or greater. 
     
     
       5. The process for producing spherical base granules comprising an easily water-soluble drug according to  claim 1  or  2 , wherein the layering liquid comprises from 5 to 20 mass % of the easily water-soluble drug and from 3 to 20 mass % of D-mannitol. 
     
     
       6. The process for producing spherical base granules comprising an easily water-soluble drug according to  claim 1  or  2 , wherein the layering liquid comprises from 1 to 15 mass % of D-mannitol.