Composition for manufacturing orally disintegrating dosage form to protect coating layer of active substance

Abstract

The present invention relates to a composition for manufacturing an orally disintegrating dosage form that is used to prevent a coating layer of an active substance which is formed in a predetermined size in order to mask a bitter taste or an unpleasant taste. A predetermined ratio of an excipient having lower hardness than the coated active substance and another excipient having higher hardness and larger particle size than the active substance are used as means for protecting the coating layer from being destroyed.

1 . A pharmaceutical composition for manufacturing an orally disintegrating dosage form, comprising: a coated active substance; a buffer having lower hardness than the coated active substance; and a shield having higher hardness and larger particle size than the coated active substance. 
     
     
         2 . The pharmaceutical composition as set forth in  claim 1 , wherein the dosage form is a tablet. 
     
     
         3 . The pharmaceutical composition as set forth in  claim 1 , wherein the hardness of the buffer is 0.1 times or more and less than 1 time as high as the hardness of the particle of the coated active substance, and the hardness of the shield is more than 1 time and 20 times or less as high as the hardness of the particle of the coated active substance. 
     
     
         4 . The pharmaceutical composition as set forth in  claim 3 , wherein the hardness of the buffer is 0.1 to 0.7 times as high as the hardness of the particle of the coated active substance, and the hardness of the shield is 4 to 15 times as high as the hardness of the particle of the coated active substance. 
     
     
         5 . The pharmaceutical composition as set forth in  claim 1 , wherein the coated active substance has the particle diameter in the range of 0.1 to 1000 the buffer has the particle diameter which is 0.1 to 10 times as large as the particle diameter of the coated active substance, and the shield has the particle size that is more than 1 time and 10 times or less as large as the particle diameter of the coated active substance. 
     
     
         6 . The pharmaceutical composition as set forth in  claim 5 , wherein the coated active substance has the particle diameter in the range of 150 to 425 μm, the buffer has the particle diameter which is 1 to 3 times as large as the particle diameter of the coated active substance and the shield has the particle diameter which is more than 1 time and 4 times or less as large as the particle diameter of the coated active substance. 
     
     
         7 . The pharmaceutical composition as set forth in  claim 1 , wherein the weight ratio of the buffer with respect to the coated active substance is 5 or less, and the weight ratio of the shield with respect to the coated active substance is 3 or less. 
     
     
         8 . The pharmaceutical composition as set forth in  claim 7 , wherein the weight of
 the above coated active substance for preparing one dosage form is in the range of 1 to 1000 mg, the weight ratio of the buffer with respect to the coated active substance is in the range of 0.1 to 3, and the weight ratio of the shield with respect to the above coated active substance is in the range of 0.1 to 2.   
     
     
         9 . The pharmaceutical composition as set forth in  claim 8 , wherein the weight ratio of the buffer with respect to the shield is at least 1. 
     
     
         10 . The pharmaceutical composition as set forth in  claim 1 , wherein the buffer or the shield is in the form of one selected from: powder; fine crystals; granules that are formed by using dry, wet, or high temperature granulation; and particles that are formed by using mounting on a neutral support body or a extrusion. 
     
     
         11 . The pharmaceutical composition as set forth in  claim 1 , wherein each of the buffer and the shield is independently manufactured by granulating a material selected from isomalt, mannitol, dried mannitol, crystalline mannitol, maltitol, lactose, glucose, lactitol, trehalose, dextrate, white sugar, white sugar for direct tableting, sorbitol, xylitol, mannitol granules, aspartame, acesulfame, acesulfame potassium, saccharin sodium, a cellulose polymer, and a mixture thereof. 
     
     
         12 . The pharmaceutical composition as set forth in  claim 1 , wherein the coating layer of the coated active substance is manufactured by: a coating method using a fluidized bed coater; a coating method using a spray drier; coagulation coating; microencapsulation; micro-granulation; ionic resin absorption process; or coating by a polymer after an active substance is applied on a seed. 
     
     
         13 . The pharmaceutical composition as set forth in  claim 1 , wherein the orally disintegrating dosage form disintegrates in an oral cavity within 60 seconds. 
     
     
         14 . The pharmaceutical composition as set forth in  claim 1 , wherein the hardness of the orally disintegrating dosage form is at least 30 N. 
     
     
         15 . The pharmaceutical composition as set forth in  claim 1 , wherein the active substance is hydrochloride itopride. 
     
     
         16 . A method of manufacturing an orally disintegrating dosage form by using the pharmaceutical composition according to  claim 1 , the method comprising:
 performing a tableting process to manufacture the orally disintegrating dosage form while such pressure as to destroy at least a portion of the buffer but not to destroy the coated active substance and the shield is applied to the pharmaceutical composition during the tableting process.