Oxcarbazepine extended release dosage form

1. An extended-release dosage form of oxcarbazepine for oral administration comprising oxcarbazepine, hydroxypropyl methylcellulose (HPMC) that has a viscosity ranging from about 50 to about 500 cP, and one or more additional pharmaceutically acceptable excipients,

wherein the dosage form is substantially free, or free of, a release promoting agent(s) and/or a polymer(s) having pH-dependent solubility,

wherein the weight percentage of HPMC is from about 20% to about 65% based upon total weight of the dosage form, and

wherein the dosage form has C max and AUCT ratios in the range of 80% to 125%, relative to an oxcarbazepine extended-release dosage form comprising a polymer having pH-dependent solubility and having a similar total amount of oxcarbazepine.

2. The dosage form of claim 1 , wherein the HMPC has a viscosity ranging from about 80 to about 120 cP.

3. The dosage form of claim 1 , wherein the oxcarbazepine used in the production of the dosage form has a particle size diameter range with a D90 of not more than about 110 μm.

4. The dosage form of claim 1 , wherein the oxcarbazepine used in the production of the dosage form has a particle size diameter range with a D50 of not more than about 55 μm.

5. The dosage form of claim 1 , wherein the oxcarbazepine used in the production of the dosage form has a particle size diameter range with a D10 of not more than about 25 μm.

6. The dosage form of claim 1 , wherein the composition is in the form of a tablet.

7. The dosage form of claim 1 , wherein the total amount of oxcarbazepine in the composition is from about 150 mg to about 600 mg of oxcarbazepine.

8. The dosage form of claim 1 , wherein the total amount of oxcarbazepine in the composition is 150 mg, 300 mg or 600 mg.

9. The dosage form of claim 1 , wherein the dosage form is substantially free of release promoting agents.

10. The dosage form of claim 1 , wherein the dosage form is free of release promoting agents.

11. The dosage form of claim 1 , when dissolution tested using USP Apparatus 1, exhibits a release profile substantially corresponding to the following pattern:

after 5 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., at least about 28% by weight of the total oxcarbazepine is released, and

after 8 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., at least about 50% by weight of the total oxcarbazepine is released.

12. The dosage form of claim 1 , wherein after 5 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., from about 28% by weight to about 53% by weight of the total oxcarbazepine is released.

13. The dosage form of claim 1 , wherein after 8 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., from about 50% by weight to about 76% by weight of the total oxcarbazepine is released.

14. The dosage form of claim 1 , when dissolution tested using USP Apparatus 1, exhibits a release profile substantially corresponding to the following pattern:

after 2 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., no more than about 25% by weight of the total oxcarbazepine is released, and

after 5 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., at least about 28% by weight of the total oxcarbazepine is released,

after 8 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., at least about 50% by weight of the total oxcarbazepine is released, and

after 16 hours at 100 rpm in 900 mL of 1% SDS in 0.05 M Sodium phosphate buffer, pH 6.8, at a temperature of 37° C.±0.5° C., not less than about 80% by weight of the total oxcarbazepine is released.

15. A method of making an extended-release dosage form of oxcarbazepine having bioequivalence to an oxcarbazepine extended-release dosage form comprising a polymer having pH-dependent solubility and having a similar total amount of oxcarbazepine in the dosage form, comprising:

mixing and milling oxcarbazepine, hydroxypropyl methylcellulose having viscosity ranging from about 50 to about 500 cP, and one or more pharmaceutically acceptable excipients to provide a mixture, wherein the mixture is substantially free, or free of, a release promoting agent(s) and/or a polymer(s) having pH-dependent solubility, wherein the weight percentage of HPMC is from about 20% to about 65% based upon total weight of the dosage form; and

compressing the mixture into tablets,

wherein the dosage form has C max and AUCT ratios in the range of 80% to 125%, relative to an oxcarbazepine extended-release dosage form comprising a polymer having pH-dependent solubility and having a similar total amount of oxcarbazepine.

16. The method of claim 15 , wherein the one or more pharmaceutically acceptable excipients excludes release promoting agents.

17. A method of treating epileptic seizures, comprising administering, to a person in need thereof, the extended release dosage form of claim 1 , in an amount effective to reduce the incidence and/or severity of the epileptic seizures.

18. The method of claim 17 , wherein the amount effective is 150 mg per day.

19. The method of claim 17 , wherein the amount effective is 300 mg per day.

20. The method of claim 17 , wherein the effective amount is 600 mg.

21. The method of claim 17 , wherein the extended release dosage form is administered once daily.

22. A method of making an extended release dosage form of oxcarbazepine of claim 1 , comprising:

mixing and milling oxcarbazepine, hydroxypropyl methylcellulose, and one or more pharmaceutically acceptable excipients to provide a mixture; and compressing the mixture into tablets.

23. The dosage form of claim 1 , wherein the dosage form is substantially free, or free of, a polymer(s) having pH-dependent solubility.