Controlled release and taste masking oral pharmaceutical composition

Abstract

Controlled release and taste masking compositions containing one or more active principles inglobated in a three-component matrix structure, i.e. a structure formed by successive amphiphilic, lipophilic or inert matrices and finally inglobated or dispersed in hydrophilic matrices. The use of a plurality of systems for the control of the dissolution of the active ingredient modulates the dissolution rate of the active ingredient in aqueous and/or biological fluids, thereby controlling the release kinetics in the gastrointestinal tract.

What is claimed is: 
     
         1 . A solid oral formulation for enhancing release of budesonide in the colon, comprising:
 an extended release core comprising 9 mg of budesonide; and   a gastro-resistant coating to control the release of said budesonide from the solid oral formulation, wherein following oral administration of a single dose to a human, the formulation provides a mean AUC 0-t  of said budesonide in said human of about 13555.9±7816.9 (pg)(hr)/mL in 36 hour.   
     
     
         2 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the formulation provides a mean T max  of budesonide in said human of about 13.3±5.9 hours. 
     
     
         3 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the formulation provides a T max  of said budesonide in said human of from about 6 hours to about 24 hours. 
     
     
         4 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the formulation provides a mean C max  of said budesonide in said human of about 1348.8±958.8 pg/mL. 
     
     
         5 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the formulation provides a mean AUC 0-infinity  of said budesonide in said human of about 16431.2±10519.8 (pg)(hr)/mL. 
     
     
         6 . The solid oral formulation of  claim 1  being a tablet. 
     
     
         7 . The solid oral formulation of  claim 1 , wherein the gastro-resistant coating comprises one or more selected from the group consisting of an acrylic acid polymer, a methacrylic acid polymer, an acrylic acid copolymer, a methacrylic acid copolymer, and a cellulose derivative. 
     
     
         8 . The solid oral formulation of  claim 7 , wherein the gastro-resistant coating further comprises a dye. 
     
     
         9 . The solid oral formulation of  claim 8 , wherein the gastro-resistant coating further comprises a plasticizer. 
     
     
         10 . The solid oral formulation of  claim 1 , wherein said oral formulation provides extended release of budesonide in the colon effective to treat irritable bowel disease in the human. 
     
     
         11 . The solid oral formulation of  claim 10 , wherein the irritable bowel disease is ulcerative colitis. 
     
     
         12 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the oral formulation provides a systemic availability of budesonide in the colon (AUC colon ) of said human that accounts for between 84.93% and 100% of the total systemic availability (AUC t ) of budesonide in the human. 
     
     
         13 . The solid oral formulation of  claim 1 , wherein following oral administration of a single dose, the oral formulation provides a mean systemic availability of budesonide in the colon (AUC colon ) of said human of about 95.88±4.19% of the total systemic availability (AUC t ) of budesonide in the human. 
     
     
         14 . The solid oral formulation of  claim 1 , having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37° C.±2° C. at pH 7.2, wherein less than 15% of budesonide is released in 1 hour, less than 25% of budesonide is released in 2 hours, 25%-55% of budesonide is released in 4 hours, and greater than 80% of budesonide is released in 8 hours. 
     
     
         15 . The solid oral formulation of  claim 1 , having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37° C.±2° C. at pH 7.2, wherein less than 15% of budesonide is released in 1 hour, 20%-60% of budesonide is released in 4 hours, and greater than 80% of budesonide is released in 8 hours. 
     
     
         16 . A solid oral formulation for enhancing release of budesonide in the colon, comprising:
 an extended release core comprising 9 mg of budesonide; and   a gastro-resistant coating to control the release of said budesonide from the solid oral formulation, wherein following oral administration of a single dose to a human, the formulation provides a mean C max  of said budesonide in said human of about 1348.8±958.8 pg/mL.   
     
     
         17 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the formulation provides a mean T max  of budesonide in said human of about 13.3±5.9 hours. 
     
     
         18 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the formulation provides a T max  of said budesonide in said human of from about 6 hours to about 24 hours. 
     
     
         19 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the formulation provides a mean AUC 0-t  of said budesonide in said human of about 13555.9±7816.9 (pg)(hr)/mL in 36 hour. 
     
     
         20 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the formulation provides a mean AUC 0-infinity  of said budesonide in said human of about 16431.2±10519.8 (pg)(hr)/mL. 
     
     
         21 . The solid oral formulation of  claim 16  being a tablet. 
     
     
         22 . The solid oral formulation of  claim 16 , wherein the gastro-resistant coating comprises one or more selected from the group consisting of an acrylic acid polymer, a methacrylic acid polymer, an acrylic acid copolymer, a methacrylic acid copolymer, and a cellulose derivative 
     
     
         23 . The solid oral formulation of  claim 22 , wherein the gastro-resistant coating further comprises a dye. 
     
     
         24 . The solid oral formulation of  claim 23 , wherein the gastro-resistant coating further comprises a plasticizer. 
     
     
         25 . The solid oral formulation of  claim 16 , wherein said oral formulation provides extended release of budesonide in the colon effective to treat irritable bowel disease in the human. 
     
     
         26 . The solid oral formulation of  claim 25 , wherein the irritable bowel disease is ulcerative colitis. 
     
     
         27 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the oral formulation provides a systemic availability of budesonide in the colon (AUC colon ) of said human that accounts for between 84.93% and 100% of the total systemic availability (AUC t ) of budesonide in the human. 
     
     
         28 . The solid oral formulation of  claim 16 , wherein following oral administration of a single dose, the oral formulation provides a mean systemic availability of budesonide in the colon (AUC colon ) of said human of about 95.88±4.19% of the total systemic availability (AUC t ) of budesonide in the human. 
     
     
         29 . The solid oral formulation of  claim 16 , having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37° C.±2° C. at pH 7.2, wherein less than 15% of budesonide is released in 1 hour, less than 25% of budesonide is released in 2 hours, 25%-55% of budesonide is released in 4 hours, and greater than 80% of budesonide is released in 8 hours. 
     
     
         30 . The solid oral formulation of  claim 16 , having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37° C.±2° C. at pH 7.2, wherein less than 15% of budesonide is released in 1 hour, 20%-60% of budesonide is released in 4 hours, and greater than 80% of budesonide is released in 8 hours.