Details for Patent: 9,592,203

Title:	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.
Inventor(s):	Villa; Roberto (Lecco, IT), Pedrani; Massimo (Gignese, IT), Ajani; Mauro (Milan, IT), Fossati; Lorenzo (Milan, IT)
Assignee:	COSMO TECHNOLOGIES LIMITED (Dublin, IE)
Filing Date:	Jul 06, 2016
Application Number:	15/202,962
Claims:	1. A tablet oral formulation for enhancing release of budesonide in the colon, consisting essentially of: a tableted extended release core comprising 9 mg of budesonide, hydroxypropyl cellulose and optionally other excipients, wherein the tableted extended release core is macroscopically homogeneous; and a gastro-resistant coating on the tableted extended release core, the gastro-resistant coating comprising a copolymer of methacrylic acid and methyl methacrylate in a 1:1 ratio, a copolymer of methacrylic acid and methyl methacrylate in a 1:2 ratio, and optionally other excipients 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.sub.0-t of said budesonide in said human of about 13555.9.+-.7816.9 (pg)(hr)/mL in 36 hours. 2. The solid oral formulation of claim 1, wherein following oral administration of a single dose, the formulation provides a mean T.sub.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.sub.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.sub.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.sub.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, wherein the gastro-resistant coating further comprises a dye. 7. The solid oral formulation of claim 6, wherein the gastro-resistant coating further comprises a plasticizer. 8. 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. 9. The solid oral formulation of claim 8, wherein the irritable bowel disease is ulcerative colitis. 10. 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.sub.colon) of said human that accounts for between 84.93% and 100% of the total systemic availability (AUC.sub.t) of budesonide in the human. 11. 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.sub.colon) of said human of about 95.88.+-.4.19% of the total systemic availability (AUC.sub.t) of budesonide in the human. 12. 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.degree. C..+-.2.degree. 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. 13. 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.degree. C..+-.2.degree. 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. 14. A tablet oral formulation A solid oral formulation for enhancing release of budesonide in the colon, consisting essentially of: a tableted extended release core comprising 9 mg of budesonide, hydroxypropyl cellulose and optionally other excipients, wherein the tableted extended release core is macroscopically homogeneous; and a gastro-resistant coating on the tableted extended release core, the gastro-resistant coating comprising a copolymer of methacrylic acid and methyl methacrylate in a 1:1 ratio, a copolymer of methacrylic acid and methyl methacrylate in a 1:2 ratio, and optionally other excipients 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.sub.max of said budesonide in said human of about 1348.8.+-.958.8 pg/mL. 15. The solid oral formulation of claim 14, wherein following oral administration of a single dose, the formulation provides a mean T.sub.max of budesonide in said human of about 13.3.+-.5.9 hours. 16. The solid oral formulation of claim 14, wherein following oral administration of a single dose, the formulation provides a T.sub.max of said budesonide in said human of from about 6 hours to about 24 hours. 17. The solid oral formulation of claim 14, wherein following oral administration of a single dose, the formulation provides a mean AUC.sub.0-infinity of said budesonide in said human of about 16431.2.+-.10519.8 (pg)(hr)/mL. 18. The solid oral formulation of claim 14, wherein the gastro-resistant coating further comprises a dye. 19. The solid oral formulation of claim 18, wherein the gastro-resistant coating further comprises a plasticizer. 20. The solid oral formulation of claim 14, wherein said oral formulation provides extended release of budesonide in the colon effective to treat irritable bowel disease in the human. 21. The solid oral formulation of claim 20, wherein the irritable bowel disease is ulcerative colitis. 22. The solid oral formulation of claim 14, wherein following oral administration of a single dose, the oral formulation provides a systemic availability of budesonide in the colon (AUC.sub.colon) of said human that accounts for between 84.93% and 100% of the total systemic availability (AUC.sub.t) of budesonide in the human. 23. The solid oral formulation of claim 14, wherein following oral administration of a single dose, the oral formulation provides a mean systemic availability of budesonide in the colon (AUC.sub.colon) of said human of about 95.88.+-.4.19% of the total systemic availability (AUC.sub.t) of budesonide in the human. 24. The solid oral formulation of claim 14, having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37.degree. C..+-.2.degree. 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. 25. The solid oral formulation of claim 14, having an in vitro dissolution profile in a buffered solution using USP II apparatus at a temperature of 37.degree. C..+-.2.degree. 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.