Claims for Patent: 8,617,600

Summary for Patent: 8,617,600

Title:	Modified release preparations containing oxcarbazepine and derivatives thereof
Abstract:	Controlled-release preparations of oxcarbazepine and derivatives thereof for once-a-day administration are disclosed. The inventive compositions comprise solubility- and/or release enhancing agents to provide tailored drug release profiles, preferably sigmoidal release profiles. Methods of treatment comprising the inventive compositions are also disclosed.
Inventor(s):	Bhatt; Padmanabh P. (Rockville, MD), Kidane; Argaw (Montgomery Village, MD), Edwards; Kevin (Lovettsville, VA)
Assignee:	Supernus Pharmaceuticals, Inc. (Rockville, MD)
Application Number:	13/476,337
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,617,600
Patent Claims:	1. A solid oral pharmaceutical formulation for once-a-day administration of oxcarbazepine comprising a homogeneous matrix comprising: (a) oxcarbazepine; (b) 1-50%, by weight of the formulation, a matrix-forming polymer selected from the group consisting of cellulosic polymers, alginates, gums, cross-linked polyacrylic acid, carageenan, polyvinyl pyrrolidone, polyethylene oxides, and polyvinyl alcohol; (c) 1-80%, by weight of the formulation, at least one agent that enhances the solubility of oxcarbazepine selected from the group consisting of surface active agents, complexing agents, cyclodextrins, pH modifying agents, and hydration promoting agents; (d) 10-90%, by weight of the formulation, at least one release promoting agent comprising a polymer having pH-dependent solubility selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetate phthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, Eudagrit L100-55 (Methacrylic Acid--Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid copolymers, wherein, in vitro: (i) between 20 and 74% of the total oxcarbazepine is released by 2 hours; and (ii) between 44 and 96% of the total oxcarbazepine is released by 4 hours. 2. The formulation of claim 1, wherein the agent that enhances the solubility of oxcarbazepine is selected from the group consisting of surface active agents, complexing agents, and pH modifying agents. 3. The formulation of claim 1, wherein the surface active agents comprise sodium docusate, sodium lauryl sulfate, sodium stearyl fumarate, polyethylene oxide (PEO) modified sorbitan monoesters, fatty acid sorbitan esters, polyethylene oxide-polypropylene oxide-(poly(ethylene oxide)) block copolymers, or combinations thereof. 4. The formulation of claim 1, wherein the matrix-forming polymer is selected from the group consisting of cellulosic polymers, alginates, cross-linked polyacrylic acid, polyvinyl pyrrolidone, polyethylene oxides, and polyvinyl alcohol. 5. The formulation of claim 1, wherein the cellulosic polymers are selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), methylcellulose (MC), powdered cellulose, cellulose acetate, sodium carboxymethylcellulose, calcium salt of carboxymethylcellulose, and ethylcellulose. 6. The formulation of claim 1, wherein the release-promoting agent is selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxycellulose phthalate, polyvinylacetate phthalate, styrene-maleic mono-ester copolymer, and Eudragit L100-55 (Methacrylic Acid--Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid copolymers. 7. The pharmaceutical formulation of claim 1, wherein the amount of oxcarbazepine is effective to produce a steady state blood level of monohydroxy derivative of oxcarbazepine in the range of about 2 .mu.g/ml to about 10 .mu.g/ml. 8. The pharmaceutical formulation of claim 1, wherein the formulation is effective in minimizing fluctuations between C.sub.min and C.sub.max of monohydroxy derivative of oxcarbazepine. 9. The pharmaceutical formulation of claim 8, which provides C.sub.max levels of monohydroxy derivative of oxcarbazepine in the range of about 6 .mu.g/ml to about 10 .mu.g/ml and C.sub.min levels of monohydroxy derivative of oxcarbazepine in the range of about 2 .mu.g/ml to about 5 .mu.g/ml. 10. The formulation of claim 1, wherein the amount of oxcarbazepine is 600 mg. 11. The pharmaceutical formulation of claim 1 in the form of pellets, tablets, granules or capsules. 12. The formulation of claim 11 in the form of tablets. 13. The formulation of claim 12, wherein each tablet comprises 600 mg of oxcarbazepine. 14. The formulation of claim 1, further comprising a lubricant selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, stearic acid, polyethylene glycol, leucine, glyceryl behenate, sodium stearyl fumarate, hydrogenated vegetable oils, and waxes. 15. The formulation of claim 14, wherein the wax is selected from the group consisting of beeswax, camuba wax, cetyl alcohol, glyceryl stearate, glyceryl palmitate, and stearyl alcohol. 16. The formulation of claim 14, wherein the lubricant is incorporated in the amount of from 0.1% to 20% by weight of the formulation. 17. The pharmaceutical formulation of claim 1, wherein the polymer having pH-dependent solubility remains intact at pH values of below 4 and dissolves at pH values of more than 4. 18. The pharmaceutical formulation of claim 1, wherein the polymer having pH-dependent solubility dissolves at pH values of more than 5. 19. The pharmaceutical formulation of claim 1, wherein the polymer having pH-dependent solubility dissolves at pH values of more than 6. 20. The formulation of claim 1, further comprising a tabletting aid selected from the group consisting of magnesium stearate, talc, cabosil, and silicified microcrystalline cellulose. 21. The formulation of claim 20, wherein the tabletting aid is incorporated in the amount of up to 25% by weight of the formulation. 22. The formulation of claim 1, comprising a surface active agent and a tabletting aid.