Claims for Patent: 12,178,824

Summary for Patent: 12,178,824

Title:	Orodispersible formulations
Abstract:	An orodispersible formulation for contraception or hormone replacement therapy containing an estrogen and a progestogen that has sufficient hardness, disintegration time and friability.
Inventor(s):	Ryan Loughlin, Roger M. Boissonneault
Assignee:	Millicent Pharma Ltd
Application Number:	US18/046,553
Patent Claims:	1. An orodispersible solid dosage form consisting of an intragranular component and an extragranular component, wherein the intragranular component consists of an estrogen, an intragranular diluent, an intragranular binder, an intragranular disintegrant, and, optionally, at least one additional intragranular agent, wherein the extragranular component consists of an extragranular diluent, an extragranular binder, an extragranular disintegrant, and, optionally, at least one additional extragranular agent, wherein: the estrogen is in an amount of up to 0.05% w/w of the orodispersible solid dosage form; the intragranular diluent is microcrystalline cellulose and mannitol at a content of 84% w/w to 97% w/w of the intragranular component; the intragranular disintegrant is croscarmellose sodium or sodium starch glycolate at a content of 2.2% w/w to 4.5% w/w of the intragranular component; the intragranular binder is a pregelatinized starch or povidone at a content of 0.5% w/w to 6% w/w of the intragranular component; the extragranular diluent is microcrystalline cellulose and mannitol at a content of 72% w/w to 88% w/w of the extragranular component; the extragranular disintegrant is croscarmellose sodium or sodium starch glycolate at a content of 5% w/w to 12% w/w of the extragranular component; the extragranular binder is a pregelatinized starch at a content of 3.5% w/w to 12% w/w of the extragranular component; the at least one additional intragranular agent and the at least one additional extragranular agent are, independently, at least one selected from the group consisting of a progestogen, a lubricant, an antioxidant, a flavoring agent, a sweetener, and a coloring agent, wherein the intragranular component constitutes from 42% w/w to 75% w/w of the orodispersible solid dosage form, wherein the orodispersible solid dosage form disintegrates in 30 seconds or less, wherein the orodispersible solid dosage form has a hardness from 2 kp to 7 kp and a friability of 0.3% or less, and wherein a content uniformity of the estrogen in the orodispersible solid dosage form satisfies ASTM E2709/E2810. 2. The orodispersible solid dosage form of claim 1, wherein the estrogen is selected from the group consisting of ethinyl estradiol, 17β-estradiol, 17β-estradiol-3-acetate, mestranol, conjugated estrogens, estrone, and any salts or combinations thereof. 3. The orodispersible solid dosage form of claim 2, wherein the estrogen is ethinyl estradiol. 4. The orodispersible solid dosage form of claim 1, which contains the progestogen. 5. The orodispersible solid dosage form of claim 4, wherein an amount of the progestogen is 0.40% w/w to 2.2% w/w of the dosage form. 6. The orodispersible solid dosage form of claim 4, wherein the orodispersible solid dosage form contains the progestogen in an amount of 0.3 mg to 1.5 mg. 7. The orodispersible solid dosage form of claim 4, wherein the progestogen is selected from the group consisting of 17-hydroxy progesterone esters and 19-nor-17-hydroxy progesterone esters, 17-alpha-ethinyl testosterone, 17-alpha-ethinyl-19-nortestosterone (norethindrone), norethindrone acetate, norgestrel, nogestamate, desogestrel and D-17-beta-acetoxy-17-beta-ethyl-17-alpha-ethinyl-gon-4-en-3-one oxime, and combinations thereof. 8. The orodispersible solid dosage form of claim 4, wherein the progestogen is norethindrone acetate. 9. The orodispersible solid dosage form of claim 1, wherein the orodispersible solid dosage form is from 60 mg to 90 mg. 10. The orodispersible solid dosage form of claim 1, wherein the orodispersible solid dosage form has a hardness from 2 kp to 6 kp. 11. The orodispersible solid dosage form of claim 1, wherein the intragranular component constitutes 42% w/w to 55% w/w of the orodispersible solid dosage form. 12. The orodispersible solid dosage form of claim 1, wherein the content of croscarmellose sodium or sodium starch glycolate as the intragranular disintegrant is from 2.4% w/w to 4% w/w of the intragranular component. 13. The orodispersible solid dosage form of claim 1, wherein the content of pregelatinized starch as the intragranular binder is from 5% w/w to 6% w/w of the intragranular component. 14. The orodispersible solid dosage form of claim 1, wherein the estrogen is ethinyl estradiol, and wherein the intragranular component further comprises norethindrone acetate. 15. The orodispersible solid dosage form of claim 14, wherein an ethinyl estradiol content is from 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form and a norethindrone acetate content is from 1% w/w to 1.9% w/w of the orodispersible solid dosage form. 16. An orodispersible solid dosage form consisting of an intragranular component and an extragranular component, wherein the intragranular component consists of an estrogen, an intragranular diluent, an intragranular binder, an intragranular disintegrant, and, optionally, at least one additional intragranular agent, wherein the extragranular component consists of an extragranular diluent, an extragranular binder, an extragranular disintegrant, and, optionally, at least one additional extragranular agent, wherein the estrogen is in an amount of up to 0.05% w/w of the orodispersible solid dosage form, wherein the intragranular diluent and the extragranular diluent is microcrystalline cellulose and mannitol, and a total content thereof is from 82% w/w to 89% w/w of the orodispersible solid dosage form, wherein the intragranular binder is pregelatinized starch or povidone and the extragranular binder is pregelatinized starch, and a total content thereof is from 4.5% w/w to 6.5% w/w of the orodispersible solid dosage form, wherein the intragranular disintegrant and the extragranular disintegrant is croscarmellose sodium or sodium starch glycolate, and a total content thereof is from 4.5% w/w to 8% w/w of the orodispersible solid dosage form, wherein the at least one additional intragranular agent and the at least one additional extragranular agent are independently at least one selected from the group consisting of a progestogen, a lubricant, an antioxidant, a flavoring agent, a sweetener, and a coloring agent, wherein the intragranular component constitutes from 42% w/w to 75% w/w of the orodispersible solid dosage form, wherein the orodispersible solid dosage form disintegrates in 30 seconds or less, wherein the orodispersible solid dosage form has a hardness from 2 kp to 7 kp and a friability of 0.3% or less, and wherein a content uniformity of the estrogen in the orodispersible solid dosage form satisfies ASTM E2709/E2810. 17. The orodispersible solid dosage form of claim 16, wherein the estrogen is selected from the group consisting of ethinyl estradiol, 17β-estradiol, 17β-estradiol-3-acetate, mestranol, conjugated estrogens, estrone, and any salts or combinations thereof. 18. The orodispersible solid dosage form of claim 17, wherein the estrogen is ethinyl estradiol. 19. The orodispersible solid dosage form of claim 16, wherein the intragranular component constitutes 42% w/w to 55% w/w of the orodispersible solid dosage form. 20. The orodispersible solid dosage form of claim 19, wherein an ethinyl estradiol content is 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form. 21. The orodispersible solid dosage form of claim 16, which contains norethindrone acetate. 22. The orodispersible solid dosage form of claim 21, wherein a norethindrone acetate content is 1% w/w to 1.9% w/w of the orodispersible solid dosage form. 23. The orodispersible solid dosage form of claim 16, wherein: the estrogen is in the amount from 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form, and the estrogen is ethinyl estradiol; a content of microcrystalline cellulose and mannitol in the intragranular component is from 86% w/w to 95% w/w of the intragranular component; a content of croscarmellose sodium or sodium starch glycolate in the intragranular component is from 2% w/w to 4% w/w of the intragranular component; a content of pregelatinized starch or povidone in the intragranular component is from 1% w/w to 5.5% w/w of the intragranular component; a content of microcrystalline cellulose and mannitol in the extragranular component is from 75% w/w to 87% w/w of the extragranular component; a content of croscarmellose sodium or sodium starch glycolate in the extragranular component is from 6% w/w to 11% w/w of the extragranular component; and a content of pregelatinized starch in the extragranular component is from 4% w/w to 10% w/w of the extragranular component. 24. The orodispersible solid dosage form of claim 16, wherein: the estrogen is in the amount from 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form, and the estrogen is ethinyl estradiol; a content of microcrystalline cellulose and mannitol in the intragranular component is from 87% w/w to 90% w/w of the intragranular component; a content of croscarmellose sodium or sodium starch glycolate in the intragranular component is from 2.3% w/w to 4% w/w of the intragranular component; a content of pregelatinized starch in the intragranular component is from 5% w/w to 5.5% w/w of the intragranular component; a content of microcrystalline cellulose and mannitol in the extragranular component is from 80% w/w to 85% w/w of the extragranular component; a content of croscarmellose sodium in the extragranular component is from 7% w/w to 11% w/w of the extragranular component; and a content of pregelatinized starch in the extragranular component is from 4.5% w/w to 5% w/w of the extragranular component. 25. The orodispersible solid dosage form of claim 1, wherein: the estrogen is in the amount from 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form, and the estrogen is ethinyl estradiol; the content of microcrystalline cellulose and mannitol in the intragranular component is from 86% w/w to 95% w/w of the intragranular component; the content of croscarmellose sodium or sodium starch glycolate in the intragranular component is from 2.2% w/w to 4% w/w of the intragranular component; the content of pregelatinized starch or povidone in the intragranular component is from 1% w/w to 5.5% w/w of the intragranular component; the content of microcrystalline cellulose and mannitol in the extragranular component is from 75% w/w to 87% w/w of the extragranular component; the content of croscarmellose sodium or sodium starch glycolate in the extragranular component is from 6% w/w to 11% w/w of the extragranular component; and the content of pregelatinized starch in the extragranular component content is from 4% w/w to 10% w/w of the extragranular component. 26. The orodispersible solid dosage form of claim 1, wherein: the estrogen is in the amount from 0.025% w/w to 0.035% w/w of the orodispersible solid dosage form, and the estrogen is ethinyl estradiol; the content of microcrystalline cellulose and mannitol in the intragranular component is from 87% w/w to 90% w/w of the intragranular component; the content of croscarmellose sodium or sodium starch glycolate in the intragranular component is from 2.3% w/w to 4% w/w of the intragranular component; the content of pregelatinized starch in the intragranular component is from 5% w/w to 5.5% w/w of the intragranular component; the content of microcrystalline cellulose and mannitol in the extragranular component is from 80% w/w to 85% w/w of the extragranular component; the content of croscarmellose sodium in the extragranular component is from 7% w/w to 11% w/w of the extragranular component; and the content of pregelatinized starch in the extragranular component is from 4.5% w/w to 5% w/w of the extragranular component. 27. The orodispersible solid dosage form of claim 16, wherein the estrogen is ethinyl estradiol, and wherein the intragranular component contains norethindrone acetate. 28. The orodispersible solid dosage form of claim 1, which is a coated orodispersible tablet. 29. The orodispersible solid dosage form of claim 1, which is an uncoated orodispersible tablet. 30. The orodispersible solid dosage form of claim 16, which is an uncoated orodispersible tablet.