Intraoral quickly disintegrating tablets

Abstract

The present invention provides an intraoral quickly disintegrating tablet containing a phosphodiesterase inhibitor having an effect of improving the erectile dysfunction and a method for manufacturing the tablet. The present invention also provides an intraoral quickly disintegrating tablet containing a slightly soluble pharmaceutical agent having an improved solubility and a method for manufacturing the tablet. That is, it is an intraoral quickly disintegrating tablet containing a cyclic GMP phosphodiesterase inhibitor and a saccharide, and a method for manufacturing the tablet. Further, it is a method for manufacturing an intraoral quickly disintegrating tablet, which comprises dissolving a slightly soluble pharmaceutical agent in an organic solvent or an aqueous organic solvent together with a surfactant and/or a water-soluble polymer, coating the solution on a filler or granulating it with a filler to obtain molded products, mixing a saccharide with them, adding an organic solvent, water or an aqueous organic solvent thereto, followed by kneading, and subjecting it to a compression-molding.

1 . An intraoral quickly disintegrating tablet comprising a difficultly soluble pharmaceutical agent and a saccharide and further comprising at least one selected from surfactant and a water-soluble polymer.  
     
     
         2 . A method for manufacturing the tablet as claimed in  claim 1 , which comprises dissolving a difficultly soluble pharmaceutical agent in an organic solvent or an aqueous organic solvent together with at least one selected from a surfactant and a water-soluble polymer, coating the solution on a filler or granulating it with a filler to obtain molded products, mixing a saccharide with them, adding an organic solvent, water or an aqueous organic solvent thereto, followed by kneading, and subjecting it to a compression-molding.  
     
     
         3 . A method for manufacturing the tablet as claimed in  claim 1 , which comprises adding at least one selected from a surfactant and a water-soluble polymer and a saccharide to a difficultly soluble pharmaceutical agent, followed by mixing, adding an organic solvent, water or an aqueous organic solvent thereto, followed by kneading, and subjecting it to a compression-molding.  
     
     
         4 . The method for manufacturing as claimed in  claim 2 , wherein the molded products are granules, fine granules or powder.  
     
     
         5 . The method for manufacturing as claimed in  claim 2 , in which the granulation-molding is carried out, using a fluidized bed granulator, a tumbling granulator, an extrusion granulator or a spray-drying granulator.  
     
     
         6 . The method for manufacturing as claimed in  claim 2  or  3 , which comprises filling the powder kneaded with the organic solvent, water or the aqueous organic solvent in a mold and subjecting it to compression-molding with a film in the compression-molding stage.  
     
     
         7 . The tablet as claimed in  claim 1 , wherein the slightly soluble pharmaceutical agent is a cyclic GMP phosphodiesterase inhibitor.  
     
     
         8 . The method for manufacturing as claimed in  claim 2  or  3 , wherein the slightly soluble pharmaceutical agent is a cyclic GMP phosphodiesterase inhibitor.  
     
     
         9 . The tablet as claimed in  claim 7 , wherein the cyclic GMP phosphodiesterase inhibitor is selected from the group consisting of: 
 5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one represented the formula (I)                          1,3-dimethyl-6-(2-propoxy-5-methanesulfonamidophenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one represented by the formula (II)                          2-(4-carboxypiperidino)-4-(3,4-methylenedioxybenzyl)amino-6-chloroquinazoline represented by the formula (III)                          (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2′,1′:6,1]pyrido[3,4-b]-indol-1,4-dione represented by the formula (IV)                          (3S,6R,12aR)-2,3,6,7,12,12a-hexahydro-2,3-dimethyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2′,1′:6,1]pyrido[3,4-b]-indol-1,4-dione shown by the formula (V)                        or a pharmacologically acceptable salt thereof.      
     
     
         10 . The method as claimed in  claim 7 , which comprises filling the kneaded mixture in a mold and subjecting it to a compression-molding with a film.  
     
     
         11 . The tablet as claimed in  claim 10 , wherein the cyclic GMP phosphodiesterase inhibitor is a compound selected from the group consisting of: 
 4-(3-chloro-4-methoxybenzyl)amino-6-cyano-1-(4-hydroxypiperidino) phthalazine hydrochloride represented by the formula (IX)                          4-(3-chloro-4-methoxyphenethyl)amino-6-cyano-1-(4-hydroxypiperidino)phthalazine hydrochloride represented by the formula (X)                          4-[(3-chloro-4-methoxybenzyl)amino]-1-(2-hydroxy-7-azaspiro[3,5]non-7-yl)-6-phthalazine carbonitrile hydrochloride represented by the formula (XI)                          1-(2-hydroxy-7-azaspiro[3,5]non-7-yl)-4-[(4-methoxy-3-methylbenzyl)amino]-6-phthalazine carbonitrile hydrochloride represented by the formula (XII)                          1-[4-fluoro-4-(hydroxymethyl)piperidino]-4-[(4-methoxy-3-methylbenzyl)amino]-6-phthalazine carbonitrile hydrochloride represented by the formula (XIII)                          4-[(3-chloro-4-methoxyphenethyl)amino]-1-(2-hydroxy-7-azaspiro[3,5]non-7-yl)-6-phthalazine carbonitrile hydrochloride shown by the formula (XIV)                          4-[(3-chloro-4-methoxybenzyl)amino]-1-(3-oxo-2-oxa-8-azaspiro[4,5]decen-8-yl)-6-phthalazine carbonitrile represented by the formula (XV)                          
     
     
         12 . The tablet as claimed in  claim 1 , wherein the saccharide is at least one selected from mannitol, sucrose, lactose, trehalose, xylitol, erythritol, glucose, starch and dextrin.  
     
     
         13 . The method for manufacturing as claimed in  claim 12 , wherein the cyclic GMP phosphodiesterase inhibitor is selected from the group consisting of: 
 5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one represented by the formula (I), and    a compound represented by the formula (VI),    or pharmacologically acceptable salts thereof.