Details for Patent: 7,910,131
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Title: | Method of treating seizures using modified release formulations of oxcarbazepine |
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) |
Filing Date: | Aug 27, 2008 |
Application Number: | 12/230,276 |
Claims: | 1. A method of treating seizures comprising administering to a subject in need thereof a pharmaceutical formulation comprising a homogeneous matrix comprising: (a) oxcarbazepine; (b) 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) 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; and (d) 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, and Eudragit L100-55 (Methacrylic Acid-Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid copolymers. 2. The method 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. 3. The method 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. 4. The method of claim 1, wherein the release promoting agent is incorporated in an amount from 10% to 90% by weight of the formulation, and the agent that enhances the solubility of oxcarbazepine is incorporated in an amount from 1% to 80% by weight of the formulation. 5. The method of claim 4, wherein the release promoting agent is incorporated in an amount from 30% to 70% by weight of the formulation, and the agent that enhances the solubility of oxcarbazepine is incorporated in an amount from 1% to 80% by weight of the formulation. 6. The method 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. 7. The method of claim 1, wherein the formulation is effective in minimizing fluctuations between C.sub.min and C.sub.max of monohydroxy derivative of oxcarbazepine. 8. The method of claim 7, 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. 9. The method of claim 1, wherein the amount of oxcarbazepine in the formulation is 600 mg. 10. The method of claim 1, wherein the formulation is in the form of pellets, tablets, granules or capsules. 11. The method of claim 10, wherein the formulation is in the form of tablets. 12. The method of claim 11, wherein each tablet comprises 600 mg of oxcarbazepine. 13. The method of claim 1, wherein the matrix-forming polymer is present in the amount of 1% to 50% by weight of the formulation. 14. The method of claim 1, wherein the formulation further comprises 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 method of claim 14, wherein the wax is selected from the group consisting of beeswax, carnuba wax, cetyl alcohol, glyceryl stearate, glyceryl palmitate, and stearyl alcohol. 16. The method of claim 14, wherein the lubricant is incorporated in the formulation in an amount of from 0.1% to 20% by weight of the formulation. 17. The method 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 method of claim 1, wherein the polymer having pH-dependent solubility dissolves at pH values of more than 5. 19. The method of claim 1, wherein the polymer having pH-dependent solubility dissolves at pH values of more than 6. 20. The method of claim 1, wherein the formulation comprises HPMC and polyvinyl pyrrolidone as matrix-forming polymers; sodium lauryl sulfate as the agent that enhances the solubility of oxcarbazepine, and Eudragit L100-55 (Methacrylic Acid-Ethyl Acrylate Copolymer (1:1)) as the release promoting agent. 21. The method of claim 1, wherein the formulation is administered once a day. 22. The method of claim 1, wherein the seizure is an epileptic seizure. 23. The method of claim 22, wherein the epileptic seizure is a partial seizure or a generalized tonic-clonic seizure. 24. The method of claim 1, wherein the patient is an adult or child. |