Pharmaceutical superdisintegrant

Abstract

Superdisintegrants which provide improved compressibility compared to prior art superdisintegrants and which does not negatively impact the compressibility of formulations which include high-dose drugs, and methods for obtaining the same are disclosed. The superdisintegrants include a particulate agglomerate of coprocessed starch or cellulose and a sufficient amount of an augmenting agent to increase the compactibility of the superdisintegrant. The augmented superdisintegrant provides a fast disintegration of a solid dosage form when incorporated in sufficient quantity therein, without untowardly affecting the compactibility of the solid dosage form (relative to the solid dosage form without the superdisintegrant).

1 . A method for improving the compressibility of a superdisintegrant, comprising: 
 causing a partial or complete internal co-transformation of superdisintegrant particles, comprising:    a) temporarily opening up said particles; and    b) adding an augmenting agent which enhances the properties of the superdisintegrant relative to the unmodified particles of the superdisintegrant.    
     
     
         2 . The method of  claim 1 , further comprising: 
 reducing elasticity of said superdisintegrant particles by making the core of said particles more hydrophobic.    
     
     
         3 . The method of  claim 1 , wherein said superdisintegrant particles are selected from the group consisting of starch materials and cellulosic materials.  
     
     
         4 . The method of  claim 1 , wherein said superdisintegrant particles are selected from the group consisting of sodium carboxymethyl starch cross-linked and sodium carboxymethylcellulose cross-linked.  
     
     
         5 - 42 . (canceled)  
     
     
         43 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, 
 comprising:    a) preparing a heated colloidal solution of an augmenting agent;    b) adding to said solution a starch-based or cellulose-based superdisintegrant to form a stirrable suspension at a temperature sufficient to allow said superdisintegrant to swell without bursting, to obtain an augmented superdisintegrant co-transformation product.    
     
     
         44 . The method of  claim 43 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         45 . The method of  claim 44 , wherein after a stirrable suspension is obtained, a suitable amount of a further augmenting agent is added.  
     
     
         46 . The method of  claim 44 , wherein said augmenting agent is a binder.  
     
     
         47 . The method of  claim 44 , wherein said augmenting agent is a lubricant.  
     
     
         48 . The method of  claim 44 , wherein said augmenting agent is selected from the group consisting of a soluble polymer, a surfactant, oils and mixtures thereof.  
     
     
         49 . The method of  claim 44 , wherein said soluble polymer is selected from the group consisting of maltodextrin and polyvinylpyrrolidone.  
     
     
         50 . The method of  claim 44 , wherein said surfactant is selected from the group consisting of polaxamer and sodium laurel sulfate.  
     
     
         51 . The method of  claim 44 , wherein said oil is selected from the group consisting of stearic acid, glyceryl behenate and magnesium stearate.  
     
     
         52 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, comprising: 
 a) preparing a colloidal solution of an augmenting agent selected from the group consisting of a soluble polymer, a surfactant, an oil, and mixtures thereof; and    b) adding a starch-based or cellulose-based superdisintegrant to form a stirrable suspension at a temperature sufficient to allow said superdisintegrant to swell without bursting, to obtain an augmented superdisintegrant co-transformation product.    
     
     
         53 . The method of  claim 52 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         54 - 60 . (canceled)  
     
     
         61 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, 
 comprising:    a) preparing a suspension of a starch-or cellulose-based superdisintegrant material to a temperature sufficient to allow said superdisintegrant to swell without bursting; and    b) adding a suitable amount of an augmenting agent, to obtain an augmented superdisintegrant cotransformation product.    
     
     
         62 . The method of  claim 61 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         63 - 69 . (canceled)  
     
     
         70 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, comprising: 
 a) preparing a hot colloidal solution of an augmenting agent selected from the group consisting of a) soluble polymers selected from the group consisting maltodextrin and polyvinylpyrollidone; b) surfactants selected from the group consisting of poloxamer and sodium laurel sulfate; c) oils selected from the group consisting of stearic acid, glyceryl behenate and magnesium stearate; or d) mixtures thereof; and    b) adding a suitable amount of said starch- or cellulose-based superdisintegrant material to form a stirrable suspension at a temperature sufficient to allow a starch-based or cellulose-based superdisintegrant to swell without bursting, to obtain an augmented superdisintegrant cotransformation product.    
     
     
         71 . The method of  claim 70 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         72 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, comprising: 
 a) preparing a solution of an augmenting agent in an aqueous solvent; and    b) adding to said solution a starch-based or cellulose-based superdisintegrant to form a stirrable suspension to allow said superdisintegrant to swell without bursting, to obtain an augmented superdisintegrant co-transformation product.    
     
     
         73 . The method of  claim 72 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         74 . The method of  claim 73 , wherein after a stirrable suspension is obtained, a suitable amount of a further augmenting agent is added.  
     
     
         75 - 80 . (canceled)  
     
     
         81 . A method of obtaining a highly compactible, superdisintegrating drug-ready complex, comprising: 
 a) preparing a solution of an augmenting agent in an aqueous solvent; and    b) adding to said solution a starch-based or cellulose-based superdisintegrant to form a stirrable suspension to allow said superdisintegrant to swell without bursting, to obtain an augmented co-transformation product.    
     
     
         82 . The method of  claim 81 , further comprising: 
 a) filtering said stirrable suspension; and    b) drying said stirrable suspension.    
     
     
         83 - 89 . (canceled)  
     
     
         90 . An augmented superdisintegrant, comprising a particulate agglomerate of coprocessed starch-based or cellulose-based superdisintegrant and a sufficient amount of an augmenting agent to increase the compactibility of a superdisintegrant, said augmented superdisintegrant providing a fast disintegration of a solid dosage form without untowardly affecting the compactibility of said solid dosage form.  
     
     
         91 . The augmented superdisintegrant of  claim 90 , wherein said starch-based or said cellulose-based superdisintegrant and said augmenting agent are in intimate association with each other, such that said augmenting agent is incorporated into the structure of said superdisintegrant particles.  
     
     
         92 . The augmented superdisintegrant of  claim 90 , wherein said augmenting agent creates physical barriers between layers of starch granules of said starch-based superdisintegrants, or opens up the fibrils of said cellulose-based superdisintegrants so that discrete molecular layers no longer exists.  
     
     
         93 . A solid dosage form comprising a therapeutically active agent in admixture with, and compressed together with, an augmented superdisintegrant.  
     
     
         94 . The solid dosage form of  claim 93 , wherein said augmented superdisintegrant comprises a starch-based or cellulose-based superdisintegrant and an augmenting agent.  
     
     
         95 . The solid dosage form of  claim 93 , wherein said solid dosage form is an oral solid dosage form, and said augmented superdisintegrant is incorporated in an amount sufficient to cause said solid dosage form to undergo a fast disintegration when exposed to aqueous fluids, either in-vitro or in-vivo.  
     
     
         96 - 97 . (canceled)  
     
     
         98 . The solid dosage form of  claim 93 , wherein said active agent and said augmented superdisintegrant have been subjected to a wet granulation procedure and thereafter compressed into said solid dosage form.  
     
     
         99 . The solid dosage form of  claim 93 , wherein said augmented superdisintegrant is incorporated into said solid dosage form in an amount from about 0.1 to about 10 percent, by weight.  
     
     
         100 . The solid dosage form of  claim 93 , wherein said augmented superdisintegrant is incorporated into said solid dosage form in an amount from about 2 to about 5 percent, by weight.