High-purity composition comprising (7a,17a)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one and a process for purifying (7a,17a)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one
The invention pertains to a process for the preparation of a high-purity composition of (7α, 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one. The process provides for a composition with less than 0.5% of (7α, 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-4-en-20-yn-3-one. This composition can be used as a source for the preparation of stable pharmaceutical dosage units.
1 - 30 . (canceled)
31 . A dosage unit comprising a pharmaceutically suitable solid carrier and an amount of (7α, 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one (tibolone), wherein the dosage unit contains less than 2% by weight of (7α, 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-4-en-20-yn-3-one relative to the tibolone after storage, at a temperature of 25° C. and a relative humidity of 60%, for 1.5 years, wherein the water content of a granulate of the dosage unit is between 5.5% and 6.5%.
32 . The dosage unit of claim 31 , wherein the (7α, 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-4-en-20-yn-3-one is present at less than 0.25% by weight relative to the tibolone.
33 . The dosage unit of claim 31 , wherein the 17α)-17-hydroxy-7-methyl-19-nor-17-pregn-4-en-20-yn-3-one is present at less than 0.1% by weight relative to the tibolone.
34 . The dosage unit of claim 31 , wherein the dosage unit includes 2.50 mg of tibolone.
35 . The dosage unit of claim 34 , wherein the dosage unit is a tablet.
36 . The dosage unit of claim 34 , wherein the dosage unit is a capsule.
37 . The dosage unit of claim 31 , wherein the dosage unit includes 1.25 mg of tibolone.
38 . The dosage unit of claim 37 , wherein the dosage unit is a tablet.
39 . The dosage unit of claim 37 , wherein the dosage unit is a capsule.
40 . The dosage unit of claim 31 , wherein the dosage unit includes 0.625 mg of tibolone.
41 . The dosage unit of claim 40 , wherein the dosage unit is a tablet.
42 . The dosage unit of claim 40 , wherein the dosage unit is a capsule.
43 . The dosage unit of claim 31 , wherein the dosage unit is formed from a granulation comprising a diluent, a disintegrant, and a binder mixed with the tibilone.
44 . The dosage unit of claim 43 , wherein the tibilone is allowed to age for at least 24 hours in the presence of water.
45 . The dosage unit of claim 31 , wherein the tibilone was aged for at least 24 hours in the presence of water.