Chronotherapeutic dosage forms

Abstract

A chronotherapeutic pharmaceutical formulation comprising a core containing an active agent (e.g., a drug) and a surfactant and a delayed release compression coating comprising a natural or synthetic gum applied onto the surface of the core.

1 . A delayed release oral solid dosage form comprising: 
 a core comprising a therapeutically effective amount of a drug and a pharmaceutically acceptable surfactant, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said compression coating delaying the release of said drug from said dosage form until after a period of time from about 2 to about 18 hours after exposure of the dosage form to an aqueous solution.    
     
     
         2 . The delayed release oral solid dosage form of  claim 1 , wherein said surfactant is selected from the group consisting of an anionic surfactant, a cationic surfactant, an amphoteric surfactant, a non-ionic surfactant, and mixtures thereof.  
     
     
         3 . The delayed release oral solid dosage form of  claim 1 , wherein said surfactant is in an amount of from about 5 to about 50 percent by weight of the core.  
     
     
         4 . The delayed release oral solid dosage form of  claim 1 , wherein said drug is a glucocorticosteroid selected from the group consisting of prednisolone, prednisone, cortisone, hydrocortisone, methylprednisolone, betametasone, dexamethasone, triamcinolone, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         5 . The delayed release oral solid dosage form of  claim 1 , wherein said one or more natural or synthetic gums are agglomerated with a saccharide material prior to being compression coated onto said core.  
     
     
         6 . The delayed release oral solid dosage form of  claim 1 , which delays release of said drug until at least about 4 hours after exposure of the dosage form to an aqueous solution.  
     
     
         7 . The delayed release oral solid dosage form of  claim 1 , wherein said delayed release material further comprises an ionizable gel strength enhancing agent selected from the group consisting of calcium sulfate, sodium chloride, potassium sulfate, sodium carbonate, lithium chloride, tripotassium phosphate, sodium borate, potassium bromide, potassium fluoride, sodium bicarbonate, calcium chloride, magnesium chloride, sodium citrate, sodium acetate, calcium lactate, magnesium sulfate, sodium fluoride, and mixtures thereof.  
     
     
         8 . The delayed release oral solid dosage form of  claim 1 , wherein said core further comprises from about 5 to about 20 percent disintegrant, by weight.  
     
     
         9 . A delayed release oral solid dosage form comprising: 
 a core comprising a therapeutically effective amount of a drug and a pharmaceutically acceptable sufactant, and an agglomerated delayed release material compression coated onto said core, said agglomerated delayed release material comprising a gum selected from the group consisting of a homopolysaccharide, a heteropolysaccharide, and a mixture of a homopolysaccharide and a heteropolysaccharide, together with a pharmaceutically acceptable excipient, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution.    
     
     
         10 . The delayed release oral solid dosage form of  claim 9 , wherein said surfactant is in an amount of from about 5 to about 50 percent by weight of the core.  
     
     
         11 . The delayed release oral solid dosage form of  claim 9 , wherein said heteropolysaccharide gum is xanthan gum and said homopolysaccharide gum is locust bean gum.  
     
     
         12 . The delayed release oral solid dosage form of  claim 9 , wherein said drug is a glucocorticosteroid.  
     
     
         13 . The delayed release oral solid dosage form of  claim 9 , wherein said core further comprises an effective amount of disintegrant.  
     
     
         14 . A delayed release oral solid dosage form comprising: 
 a core comprising a therapeutically effective amount of a drug, an effective amount of a pharmaceutically acceptable sufactant and an effective amount of a disintegrant, and an agglomerated delayed release material compression coated onto said core, said agglomerated delayed release material consisting essentially of one or more natural or synthetic pharmaceutically acceptable gums, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution.    
     
     
         15 . The delayed release oral solid dosage form of  claim 14 , wherein said surfactant is in an amount of from about 5 to about 50 percent by weight of the core.  
     
     
         16 . The delayed release oral solid dosage form of  claim 14 , wherein said core comprises from about 5 to about 20 percent disintegrant, by weight.  
     
     
         17 . The delayed release oral solid dosage form of  claim 14 , which delays the release of said drug until at least about 4 hours after exposure of the dosage form to an aqueous solution.  
     
     
         18 . The delayed release oral solid dosage form of  claim 14 , wherein said gums comprise a mixture of xanthan gum and locust bean gum.  
     
     
         19 . A delayed release oral solid dosage form comprising: 
 a core comprising a therapeutically effective amount of a drug, a surfactant and a disintegrant, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution, said disintegrant being included in said core in an amount effective to cause the release of at least about 50 percent of said drug into said aqueous solution within one hour after said predetermined period of time.    
     
     
         20 . The delayed release oral solid dosage form of  claim 19 , wherein said surfactant is in an amount of from about 5 to about 50 percent by weight of the core.  
     
     
         21 . The delayed release oral solid dosage form of  claim 19 , wherein said disintegrant comprises from about 5 to about 20 percent of said core, by weight.  
     
     
         22 . The delayed release oral solid dosage form of  claim 19 , wherein said disintegrant comprises from about about 0.1 to about 5 percent of said oral solid dosage form, by weight.  
     
     
         23 . A delayed release oral solid tablet, comprising: 
 a tablet core comprising a therapeutically effective amount of a drug and a pharmaceutically acceptable surfactant, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said gums comprising from about 6.5 percent to about 83 percent of the tablet by weight, said compression coating delaying the release of said drug from said dosage form for a period of time from about 2 to about 18 hours after exposure of the dosage form to an aqueous solution.    
     
     
         24 . The delayed release oral solid dosage form of  claim 23 , wherein said surfactant is in an amount of from about 5 to about 50 percent by weight of the core.  
     
     
         25 . The delayed release oral solid tablet of  claim 23 , wherein said tablet core further comprises from about 5 to about 20% superdisintegrant.