Patent EA-004503-B1 (EA)
Title: Levodopa/carbidopa/entacapone pharmaceutical preparation
Inventor: KALLIOINEN SARI
IPC: A61P25/16
Filed: 2000-06-29
Abstract: 1. An oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and levodopa. 2. The composition according to claim 1, wherein entacapone and levodopa are in the form of granules and carbidopa is in powder form. 3. The composition according to claim 1, wherein entacapone and levodopa are in the form of first granules and carbidopa is in the form of second granules. 4. An oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and comprising at least one pharmaceutically acceptable excipient being a sugar alcohol or starch, or a sugar alcohol and starch. 5. The composition according to claim 4, wherein the sugar alcohol is mannitol. 6. The composition according to claim 4, wherein the starch is maize starch. 7. The composition according to claim 4, wherein the composition further comprises a hydrogenated vegetable oil. 8. The composition according to claim 7, wherein the hydrogenated vegetable oil is a hydrogenated castor oil. 9. The composition according to claim 4, wherein the composition further comprises a disintegrant. 10. The composition according to claim 9, wherein the disintegrant is croscarmellose sodium. 11. A stable oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and comprising at least one pharmaceutically acceptable excipient other than microcrystalline cellulose. 12. A method for preparing an oral solid composition comprising entacapone, levodopa and carbidopa or pharmaceutically acceptable salts or hydrates thereof, which comprises mixing first entacapone and levodopa separately, adding carbidopa separately and formulating the mixture into a plurality of dosage forms. 13. A method according to claim 12, wherein carbidopa is added in powder form extragranually to granules of entacapone and levodopa. 14. A method of claim 12, wherein carbidopa is added in a form of granules to a granule batch of entacapone and levodopa. 15. A method of claim 12 comprising: a) mixing pharmacologically effective amounts of entacapone and levodopa or a pharmaceutically acceptable salt or hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a first mixture; b) granulating the first mixture to obtain a first granule batch; c) mixing a pharmaceutically effective amount of carbidopa or a pharmaceutically acceptable salt of hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a second mixture; d) granulating the second mixture to obtain a second granule batch; e) mixing the first granule batch, the second granule batch, optionally a lubricant and optionally one or more pharmaceutically acceptable excipients to obtain a third mixture; and f) formulating the third mixture into a plurality of dosage forms. 16. A method of claim 12 comprising a) mixing pharmacologically effective amounts of entacapone and levodopa or a pharmaceutically acceptable salt or hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a first mixture; b) granulating the first mixture to obtain a granule batch; c) adding a pharmacologically effective amount of carbidopa or a pharmaceutically acceptable salt or hydrate thereof, optionally a lubricant, and optionally one or more pharmaceutically acceptable excipients to the granule batch to obtain a second mixture; d) formulating the second mixture into a plurality of dosage forms. 17. The method according to claim 15 or 16, wherein the granulation method is wet granulation. 18. An oral pharmaceutical tablet comprising 200 mg entacapone, 50-150 mg levodopa and 10-37.5 mg carbidopa and having substantially the following characteristics: weight 400-750 mg and volume dimensions for oval tablet from 200 to 1000 mm<3>. 19. An oral pharmaceutical tablet comprising 200 mg entacapone, 50-50 mg levodopa, and 10-37.5 mg carbidopa and having substantially the following characteristics: weight 400-750 mg and volume dimensions for oval tablet: length 13-18 mm; width 6-9 mm; and height 4-7 mm. 20. Method of treating a subject suffering from Parkinson's disease, which comprises administering a composition of any one of claims 1 to 11 or 18,19 to a subject in need of such treatment.