Claims for Patent: 11,617,751

Summary for Patent: 11,617,751

Title:	Pharmaceutical composition containing a tetrahydrofolic acid
Abstract:	The present invention relates to solid pharmaceutical compositions, in particular to oral contraceptives, comprising a progestogen, such as drospirenone; an estrogen, such as ethinylestradiol; a tetrahydrofolic acid or a pharmaceutically acceptable salt thereof, such as calcium 5-methyl-(6S)-tetrahydrofolate; and at least one pharmaceutical acceptable excipient or carrier. The compositions of the invention provide good stability of the tetrahydrofolic acid upon storage while still ensuring a fast and reliable release of the estrogen and the progestogen present in the composition.
Inventor(s):	Kristina King
Assignee:	Bayer Pharma AG, Bayer Intellectual Property GmbH
Application Number:	US13/721,744
Patent Claims:	1. A tablet core comprising a solid pharmaceutical composition comprising particles comprising 3 mg of drospirenone, 0.02 or 0.03 mg of ethinyl estradiol, 10-90 wt%, which is based on tablet core total weight, of microcrystalline cellulose, optionally 20-80 wt%, which is based on tablet core total weight, of lactose monohydrate, and 0.42-0.49 mg of an alkaline earth metal salt of 5-methyl-(6S)-tetrahydrofolic acid, wherein the in vitro dissolutions of drospirenone and the salt of 5-methyl-(6S)-tetrahydrofolic acid individually are such that at least 85% of each is dissolved from the composition within 30 minutes, as determined by the USP XXIX Paddle Method II by water for drospirenone and a 0.03% ascorbic acid aqueous solution, which is adjusted to pH 3.5 with 0.05 M phosphate buffer for the salt of 5-methyl-(6S)-tetrahydrofolic acid at 37° C. as the dissolution media and with 50 rpm as the stirring rate, and wherein the stability of the salt of 5-methyl-(6S)-tetrahydrofolic acid is such that at least 90% of said amount thereof is present in the composition after storage in a closed container for 12 months at 25° C. and 60% relative humidity, and wherein at least one of the following conditions is satisfied condition 1: the tablet core does not contain lactose monohydrate, condition 2: the tablet core contains non-micronized drospirenone, condition 3: the tablet core contains 50 to 90 wt% of microcrystalline cellulose, condition 4: the tablet core contains 20 to 45 wt% of lactose monohydrate, condition 5: the tablet core is in a sealed blister pack among 28 dosage units, condition 6: the tablet core is in a set of one or more sealed blister packs among 364 dosage units, condition 7: the tablet core has a sweet taste. 2. A tablet core according to claim 1, which does not contain lactose monohydrate. 3. A tablet core according to claim 1, which contains non-micronized drospirenone. 4. A tablet core according to claim 1, which contains 50 to 90 wt% of microcrystalline cellulose. 5. A tablet core according to claim 1, which contains 20 to 45 wt% of lactose monohydrate. 6. A tablet core according to claim 1, which is in a sealed blister pack among 28 dosage units. 7. A tablet core according to claim 1, which is in a set of one or more sealed blister packs among 364 dosage units. 8. A tablet core according to claim 1, which has a sweet taste. 9. A tablet core according to claim 1, which has a round shape. 10. A method for female contraception comprising administering to a female a composition according to claim 1. 11. A method for the effective alleviation of all physiological and psychological signs of estrogen deficiency comprising administering to a female a composition according to claim 1. 12. A method for the prophylactic treatment of osteoporosis comprising administering to a female a composition according to claim 1. 13. A method for the prevention of anemia comprising administering to a female a composition according to claim 1. 14. A method for the effective alleviation of all physiological and psychological signs of estrogen deficiency comprising administering to a female a composition according to claim 2. 15. A method for the prophylactic treatment of osteoporosis comprising administering to a female a composition according to claim 2. 16. A method for the prevention of anemia comprising administering to a female a composition according to claim 2. 17. A method for lessening the frequency, persistence, duration and/or severity of hot flushes, mood changes and/or anxiety comprising administering to a female a composition according to claim 1. 18. A method for prevention or alleviation of physical changes associated with estrogen deficiency, which is atrophy of the breasts, comprising administering to a female a composition according to claim 1. 19. A method for prevention or alleviation of physical changes associated with estrogen deficiency, which is changes in skin condition, comprising administering to a female a composition according to claim 1. 20. A method for treating or preventing dyspareunia, comprising administering to a female a composition according to claim 1. 21. A method for the prophylactic treatment of osteoporosis comprising administering to a female a composition according to claim 8. 22. A method for female contraception comprising administering to a female a composition according to claim 8. 23. A method for protecting against congenital malformations during a periconceptional period in a pregnant female, comprising administering to said female the composition according to claim 1. 24. A method for maintaining good hair distribution and thickness through peri-menopausal phase, menopause, or post-menopausal phase of a woman's life, comprising administering to said female the composition according to claim 1. 25. A tablet core according to claim 1, which has an oval shape. 26. A method for the prophylactic prevention of changes in skin condition, comprising administering to a menopausal female the composition according to claim 1. 27. A method for improving poor concentration, comprising administering to a menopausal female the composition according to claim 1. 28. A process for the manufacture of a composition according to claim 2, comprising the steps of: (i) subjecting the drospirenone, the ethinyl estradiol and the microcrystalline cellulose to a granulation process, (ii) mixing the alkaline earth metal salt of 5-methyl-(6S)-tetrahydrofolic acid with the granules formed in step (i), and (iii) optionally continuing the granulation process, and/or (iv) optionally collecting the granules. 29. A process for the manufacture of a composition according to claim 3, comprising the steps of: (i) subjecting the drospirenone, the ethinyl estradiol and the microcrystalline cellulose to a granulation process, (ii) mixing the alkaline earth metal salt of 5-methyl-(6S)-tetrahydrofolic acid with the granules formed in step (i), and (iii) optionally continuing the granulation process, and/or (iv) optionally collecting the granules.