Claims for Patent: 8,623,409

Summary for Patent: 8,623,409

Title:	Clonidine formulation
Abstract:	An oral clonidine dosage unit providing a twenty-four hour extended release profile following a single dose administration is provided. The dosage unit comprises a pharmaceutically effective amount of a coated complex comprising clonidine bound to a cationic exchange resin, which is characterized by a twenty-four hour release profile with a single peak, wherein said oral clonidine dosage unit provides a therapeutically effective plasma concentration for at least about 70%, or at least 85% of the twenty-four hour period following the single dose administration. Both liquid and solid formulations are provided, as are methods of treating a patient by a single administration of a formulation of the invention so as to achieve a therapeutic effect for 24-hours.
Inventor(s):	Mehta; Ketan (Cranbury, NJ), Tu; Yu-Hsing (West Windsor, NJ)
Assignee:	Tris Pharma Inc. (Monmouth Junction, NJ)
Application Number:	12/908,796
Patent Claims:	1. An oral clonidine liquid suspension composition having a twenty-four hour extended release profile with a single plasma concentration peak following a single oral dose, said dosage unit comprising an aqueous liquid suspension base and a pharmaceutically effective amount of cured, barrier coated, clonidine-cation exchange resin complex-matrix particles, said cured barrier coating comprising polyvinylacetate and a plasticizer and being a cured, water-permeable, high tensile strength, water-insoluble, barrier coating having an elongation factor in the range of about 150% to 400%, wherein said cured barrier coating is over the matrix comprising a hydrophilic or hydrophobic matrix forming polymer and a complex comprising clonidine bound to a cationic exchange resin in a ratio of about 1:120 to about 1:180 clonidine to cation exchange resin, wherein said liquid suspension provides a mean plasma clonidine concentration in human patients of about 0.5 ng/mL at about 6 to about 10 hours following a single clonidine dose of about 0.2 mg. 2. The oral clonidine liquid suspension according to claim 1, wherein the cured barrier coating further comprises a stabilizer. 3. The oral clonidine liquid suspension according to claim 2, wherein the cured barrier coating is present in an amount of about 10% to 70% w/w of the clonidine-cation exchange resin complex-matrix prior to coating. 4. The oral clonidine liquid suspension according to claim 2, wherein the cured barrier coating is present in an amount of about 30 to 50% w/w of the clonidine-cation exchange resin complex-matrix prior to coating. 5. The oral clonidine liquid suspension according to claim 4, wherein the cured barrier coating is present in an amount of about 40% w/w of the clonidine-cation exchange resin complex-matrix prior to coating. 6. The oral clonidine liquid suspension according to claim 1, wherein clonidine to resin ratio is about 1:150. 7. The oral clonidine liquid suspension according to claim 1, wherein the plasma half-life of clonidine is 13.7 hours.+-.3 hours. 8. The oral clonidine liquid suspension according to claim 1, wherein the barrier coating further comprises a a stabilizer and a surfactant. 9. The oral clonidine liquid suspension according to claim 1, wherein the plasticizer comprises about 2.5 to about 25% w/w of the barrier coating and is selected from the group consisting of triacetin, dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, and mixtures thereof. 10. The oral clonidine liquid suspension according to claim 8, wherein the stabilizer is polyvinylpyrrolidone and the surfactant is sodium lauryl sulfate. 11. The oral clonidine liquid suspension according to claim 10, wherein the polyvinyl pyrrolidone comprises about 5 to about 10% w/w of the barrier coating. 12. The oral clonidine liquid suspension according to claim 1, wherein the matrix forming polymer is a polymer or copolymer selected from the group consisting of a ethyl cellulose, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, polyvinyl acetate and mixtures thereof. 13. The oral clonidine liquid suspension according to claim 12, wherein the matrix forming polymer is an acrylic based polymer or copolymer. 14. The oral clonidine liquid suspension according to claim 13, wherein the matrix forming polymer is a neutral copolymer comprising ethyl acrylate and methyl methacrylate. 15. The oral clonidine liquid suspension according to claim 1, wherein the dosage unit comprises a multiplicity of coated clonidine-cation exchange resin complex-matrix particles, said coated clonidine-cation exchange resin complex-matrix particles having an average particle size in the range of 50 to 300 microns. 16. A method for delivering an effective amount of clonidine for a twenty-four hour period which provides a single peak plasma concentration, the method comprising administering to a subject a single oral clonidine liquid suspension according to claim 1 in the evening. 17. The oral clonidine liquid suspension according to claim 1 which comprises a multiplicity of coated clonidine-cation exchange resin complex-matrix particles, said coated matrix particles having an average particle size in the range of about 20 microns to about 200 microns. 18. The oral clonidine liquid suspension according to claim 1, which provides a mean plasma concentration for clonidine in human patients of about 0.49 (.+-.0.09) ng/mL at 7.8 hours (.+-.1.7 hours) following a single clonidine dose of about 0.2 mg. 19. The oral clonidine liquid suspension according to claim 1, wherein the plasma half-life of clonidine following a single dose of the composition is about 10 to about 18 hours. 20. The oral liquid suspension according to claim 19, wherein the plasma half-life of clonidine is 13.7 hours.+-.3 hours. 21. The oral liquid suspension according to claim 1, wherein the cured barrier coating is present in an amount of about 30% by weight to about 50% by weight of the clonidine-cation exchange resin complex-matrix prior to coating thereof. 22. The oral liquid suspension according to claim 1, wherein the matrix forming polymer is polyvinylpyrrolidone. 23. The oral liquid suspension according to claim 1, wherein the cured barrier coating layer comprises about 70 to 90% by weight polyvinylacetate polymer and about 2.5 to about 10% by weight plasticizer. 24. The oral liquid suspension according to claim 1, wherein the plasticizer is triacetin. 25. An oral clonidine tablet having a twenty-four hour extended release profile with a single plasma concentration peak following a single oral dose, said tablet comprising pharmaceutically acceptable excipients and a pharmaceutically effective amount of cured, barrier coated, clonidine-cation exchange resin complex-matrix particles compressed into a tablet form, said cured barrier coating being a cured, water-permeable, high tensile strength, water-insoluble, barrier coating having an elongation factor in the range of about 150% to 400% and comprising polyvinylacetate and a plasticizer, wherein said cured barrier coating is over the matrix comprising a hydrophilic or hydrophobic matrix forming polymer and a complex comprising clonidine bound to a cationic exchange resin in a ratio of about 1:120 to about 1:180 clonidine to cation exchange resin, wherein said tablet provides a mean plasma concentration for clonidine in human patients of about 0.5 ng/mL at about 6 to about 10 hours following a single clonidine dose of about 0.2 mg. 26. The oral clonidine tablet according to claim 25, which provides a mean plasma concentration for clonidine in human patients of about 0.49 (.+-.0.09) ng/mL at 7.8 hours (.+-.1.7 hours) following a single clonidine dose of about 0.2 mg. 27. The oral clonidine tablet according to claim 25, wherein the plasma half-life of clonidine following a single dose of the composition of is about 10 to about 18 hours. 28. The oral clonidine tablet according to claim 25, wherein the plasma half-life of clonidine is 13.7 hours.+-.3 hours.