Quick disintegrating tablet in buccal cavity and manufacturing method thereof

Abstract

The present invention relates to a quick-disintegrating tablet in the buccal cavity comprising a drug, a diluent, and a saccharide with a relatively lower melting point than the drug and the diluent, which is obtained by uniformly mixing the saccharide with a low melting point in the tablet so that a bridge will be formed between said drug and/or said diluent particles by the product of melting and then solidification of this saccharide with a low melting point. Moreover, the present invention relates to a method of manufacturing a quick-disintegrating tablet in the buccal cavity comprising a drug, a diluent and a saccharide with a relatively lower melting point than the drug and the diluent, which comprises (a) the process whereby tablet starting materials including a drug, a diluent, and a saccharide with a relatively lower melting point than the drug and the diluent are molded under the low pressure necessary for retaining the shape of a tablet, (b) the process whereby the molded product obtained in process (a) is heated to at least the temperature at which this saccharide with a low melting point will melt, and (c) the process whereby the molded product obtained in process (b) is cooled to at least the temperature at which the molten saccharide with a low melting point solidifies. The present invention presents a quick-disintegrating tablet in the buccal cavity that can be used for practical purposes in that it has almost the same properties as conventional oral pharmaceutical tablets, that is, it has sufficient tablet strength that it can be used with automatic unit dosing machines, and it is produced by conventional tableting machines, and a manufacturing method thereof. Moreover, the present invention presents a quick-disintegrating tablet in the buccal cavity which, in comparison to conventional quick-disintegrating tablets in the buccal cavity, has increased tablet strength and an improved friability without prolonging the disintegration time in the buccal cavity, and a manufacturing method thereof.

1 . A quick-disintegrating tablet in the buccal cavity comprising a drug, a diluent, a saccharide with a relatively lower melting point than said drug and said diluent, and a binder agent, wherein said saccharide with a lower melting point and said binder agent are uniformly mixed in the tablet, and wherein a bridge is formed between said drug and/or said diluent particles by the product of melting and then solidification of the saccharide with a low melting point.  
     
     
         2 . The quick-disinterating tablet in the buccal cavity of  claim 1 , wherein the saccharide with a low melting point is one whose melting point is at least 10° C. lower than that of the drug and diluent.  
     
     
         3 . The quick-disintegrating tablet in buccal cavity of  claim 1 , wherein the saccharide with a low melting point is one or two or more selected from the group consisting of xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, and their hydrates.  
     
     
         4 . The quick-disintegrating tablet in the buccal cavity of claims  1 , wherein the amount of saccharide with a low melting point is 0.5 to 25 w/w % in terms of the drug and/or the diluent.  
     
     
         5 . The quick-disintegrating tablet in the buccal cavity claims  1 , wherein the binder is a saccharide with high moldability that shows a tablet hardness of 2 kp or more when 150 mg saccharide are tableted under a tableting pressure of 10 to 50 kg/cm 2  using a punch with a diameter of 8 mm, and/or a water-soluble polymer.  
     
     
         6 . The quick-disintegrating tablet in the buccal cavity of claims  1 , wherein the diluent is a saccharide with a relatively higher melting point than the saccharide with a low melting point in claims  1 .  
     
     
         7 . The quick-disintegrating tablet in the buccal cavity in  claim 6 , wherein the saccharide with a high melting point in  claim 6  is one or two or more selected from the group consisting of xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, lactose, and their hydrates.  
     
     
         8 . The quick-disintegrating tablet in the buccal cavity in  claim 7 , wherein the saccharide with a high melting point in  claim 7  is one or two or more selected from the group consisting of mannitol, sucrose, lactose, and their hydrates.  
     
     
         9 . The quick-disintegrating tablet in the buccal cavity of claims  1 , wherein the saccharide with a low melting point is trehalose and/or erythritol and the saccharide with a high melting point is mannitol and/or lactose.  
     
     
         10 . The quick-disintegrating tablet in the buccal cavity in  claim 9 , wherein the saccharide with a low melting point is erythritol and the saccharide with a high melting point is mannitol.  
     
     
         11 . The quick-disintegrating tablet in the buccal cavity in  claim 5 , wherein the saccharide with high moldability and/or a water-soluble polymer is maltose, maltitol, sorbitol, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, copolyvidone, or polyvinyl alcohol.  
     
     
         12 . The quick-disintegrating tablet in the buccal cavity in  claim 11 , wherein the binder is maltitol and/or copolyvidone.  
     
     
         13 . The quick-disintegrating tablet in the buccal cavity of  claim 1 , wherein porosity is 10 to 80%.  
     
     
         14 . The quick-disintegrating tablet in the buccal cavity in  claim 13 , wherein porosity is 20 to 50%.  
     
     
         15 . The quick-disintegrating tablet in the buccal cavity of  claim 1 , where tablet hardness is 3 kp or higher and the friability is 1% or less.  
     
     
         16 . The quick-disintegrating tablet in the buccal cavity in  claim 15 , where tablet hardness is 4 kp or higher and the friability is 0.8% or less.  
     
     
         17 . The quick-disintegrating tablet in the buccal cavity in  claim 16 , wherein the friability is 0.5% or less.  
     
     
         18 . The quick-disintegrating tablet in the buccal cavity in claims  1 , wherein the amount of drug added is at least the effective amount in terms of treatment and no more than 80 w/w % tablet weight.  
     
     
         19 . A method of manufacturing a quick-disintegrating tablet in the buccal cavity comprising a drug, a diluent and a saccharide with a relatively lower melting point than said drug and said diluent, which comprises: (a) the process whereby tablet starting materials including the drug, the diluent, the saccharide with a relatively lower melting point than said drug and said diluent, and a binder agent are molded under the low pressure necessary for retaining the shape of a tablet, (b) the process whereby the molded product obtained by process (a) is heated to at least the temperature at which the saccharide with a low melting point will melt, and (c) the process whereby the molded product obtained by process (b) is cooled to at least the temperature at which the molten saccharide with a low melting point solidifies.  
     
     
         20 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19 , wherein by means of process (a) in claim  19 , the drug, the diluent, the saccharide with a relatively lower melting point than said drug and said diluent, and the binder agent are physically mixed to obtain the tablet starting materials.  
     
     
         21 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity in  claim 19 , wherein by means of process (a) in  claim 19 , the saccharide with a low melting point and the binder agent is dissolved and/or suspended in a pharmaceutically acceptable solvent and sprayed as a binder for coating and/or granulation to obtain the tablet starting materials.  
     
     
         22 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity is of  claim 19 , wherein by means of process (a) in  claim 19 , the saccharide with a low melting point is mixed with the drug and the diluent as particles and/or powder and granulation is performed using a binder solution consisting a saccharide with high moldability and/or Water-soluble polymer to obtain the tablet starting materials.  
     
     
         23 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity in  claim 19 , wherein by means of process (a) in  claim 19 , the tablet starting materials are molded under a tableting pressure of 25 to 800 kg/punch.  
     
     
         24 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity in  claim 19 , wherein by means of process (b) in  claim 19 , heating is performed at a temperature between the melting point of the saccharide with a low melting point and the melting point of the drug and diluent.  
     
     
         25 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity in of  claim 19 , which further comprises (d) the process whereby the molded product is humidified and dried, when a saccharide with low melting point becomes an amorphous saccharide by heating.  
     
     
         26 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 37 , wherein process (d) in  claim 37  is between process (a) and process (b), or after process (c).  
     
     
         27 . The quick-disintegrating tablet in the buccal cavity in  claim 1 , wherein the saccharide with low melting point is erythritol, the saccharide is lactose and/or mannitol, and saccharide with high moldability is maltitol, or wherein the saccharide with a low melting point is erythritol, the saccharide with a high melting point is lactose and/or mannitol, and water-soluble polymer is copolyvidone.  
     
     
         28 . The quick-disintegrating tablet in the buccal cavity of  claim 1 , wherein when the saccharide with a low melting point becomes an amorphous saccharide by heating, further the tablet is performed by humidifying and drying.  
     
     
         29 . The quick-disintegrating tablet in the buccal cavity in  claim 28 , wherein the saccharide with a low melting point becoming an amorphous sugar by heating is glucose, sorbitol, maltose or trehalose.  
     
     
         30 . A quick-disintegrating tablet in the buccal cavity (i) comprising (1) a drug, (2) lactose and/or mannitol, (3) erythritol, and (4) maltitol, wherein the tablet hardness is 3 kp or higher and the friability is 1% or less and porosity is approximately 30 to approximately 50%, or (ii) comprising (1) a drug, (2) lactose and/or mannitol, (3) erythritol, and (4) copolyvidone, wherein the tablet hardness is 3 kp or higher and the friability is 1% or less and porosity is approximately 30 to approximately 50%.  
     
     
         31 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19 , wherein the saccharide with a low melting point is one or 2 or more selected from the group consisting of xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, and their hydrates.  
     
     
         32 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19 , wherein the saccharide with a low melting point is one or 2 or more selected from the group consisting of xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, lactose, and their hydrates.  
     
     
         33 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19  wherein the binder is a saccharide with high moldability that shows a tablet hardness of 2 kp or more when 150 mg saccharide are tableted under a tableting pressure of 10 to 50 kg/cm 2  using a punch with a diameter of 8 mm, and/or a water-soluble polymer.  
     
     
         34 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19 , wherein the saccharide with high moldability and/or a water-soluble polymer is maltose, maltitol, sorbitol, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, copolyvidone, or polyvinyl alcohol.  
     
     
         35 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 34 , a saccharide with high moldability and/or a water-soluble polymer is maltitol and/or copolyvidone.  
     
     
         36 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 19 , wherein the saccharide with low melting point is erythritol, the saccharide is lactose and/or mannitol, and saccharide with high moldability is maltitol, or wherein the saccharide with a low melting point is erythritol, the saccharide with a high melting point is lactose and/or mannitol, and water-soluble polymer is copolyvidone.  
     
     
         37 . The method of manufacturing a quick-disintegrating tablet in the buccal cavity of  claim 25 , wherein the saccharide with a low melting point becoming an amorphous saccharide by heating is glucose, sorbitol, maltose, or trehalose.