Orally disintegrating solid dosage unit containing an estetrol component

1. An orally disintegrating solid pharmaceutical dosage unit having a weight between 50 and 1,000 mg, the dosage unit consisting of:

(a) 4-95 wt. % of granules consisting of:

(i) 3-80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof;

(ii) 20-97 wt. % C 4 -C 12 sugar alcohol; and

(iii) 0-45 wt. % of one or more pharmaceutically acceptable ingredients; and

(b) 5-96 wt. % of one or more pharmaceutically acceptable excipients;

wherein the solid dosage unit has at least 0.1 mg of the estetrol component.

2. The solid dosage unit according to claim 1 , wherein the estetrol component is estetrol.

3. The solid dosage unit according to claim 2 , wherein the estetrol is anhydrous estetrol.

4. The solid dosage unit according to claim 1 , wherein the dosage unit consists of 5 to 90 wt. % of the granules.

5. The solid dosage unit according to claim 1 , wherein the granules have a volume weighted average size between 30 and 200 μm.

6. The solid dosage unit according to claim 1 , wherein the granules have a volume weighted average size between 40 and 150 μm.

7. The solid dosage unit according to claim 1 , wherein the C 4 -C 12 sugar alcohol is selected from mannitol, erythritol, isomalt and combinations thereof.

8. The solid dosage unit according to claim 1 , wherein the one or more pharmaceutically acceptable excipients of (b) comprise particles containing a disintegrating agent dispersed in a matrix containing a C 4 -C 6 sugar alcohol, wherein the particles represent at least 30 wt. % of the one or more pharmaceutically acceptable excipients.

9. The solid dosage unit according to claim 8 , wherein the particles have 10-50 wt. % of disintegrating agent and 40-90 wt. % of C 4 -C 6 sugar alcohol.

10. The solid dosage unit according to claim 9 , wherein the disintegrating agent is selected from crospovidone, hydroxypropyl cellulose, croscarrnellose sodium, crystalline cellulose and combinations thereof.

11. The solid dosage unit according to claim 8 , wherein the C 4 -C 6 sugar alcohol is selected from mannitol, xylitol and combinations thereof.

12. The solid dosage unit according to claim 1 , wherein the pharmaceutically acceptable ingredient comprises progestogen present in an amount of 0.05-10 mg.

13. A method for female hormone replacement therapy, comprising administering sublingually, buccally or sublabially the dosage unit according to claim 1 .

14. The method according to claim 13 , wherein the administering is once daily administration.

15. A method of preparing the solid dosage unit according claim 1 , comprising:

(a) heating a blend of the estetrol component, the C 4 -C 12 sugar alcohol and the optional one or more pharmaceutically acceptable ingredients to a temperature between 160 and 240° C. to form a hot pumpable mixture;

(b) cooling down the hot pumpable mixture to solidify the C 4 -C 12 sugar alcohol to produce solid granules;

(c) mixing the solid granules with the one or more pharmaceutically acceptable excipients to form a mixture; and

(d) compacting the mixture into a solid dosage unit.

16. The method according to claim 15 , wherein the temperature is between 170 and 240° C.

17. The method according to claim 15 , wherein the temperature is between 180 and 240° C.

18. The method according to claim 15 , wherein cooling down the hot pumpable mixture comprises spray chilling to produce the solid granules.