Orally disintegrating solid dosage unit containing an estetrol component
The present invention provides an orally disintegrating solid pharmaceutical dosage unit having a weight of 50-1,000 mg and containing at least 0.1 mg of an estetrol component selected from estetrol, estetrol esters and combinations thereof. This solid dosage unit consists of: 4-95 wt. % of granules consisting of: 3-80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof; 20-97 wt. % C 4 -C 12 sugar alcohol; 0-45 wt. % of one or more other pharmaceutically acceptable ingredients; and 5-96 wt. % of one or more pharmaceutically acceptable excipients. The solid dosage units of the present invention are particularly suited for sublingual, buccal or sublabial administration of the estetrol component.
1. A method for contraception, comprising administering to a mammalian female sublingually, buccally or sublabially 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 method according to claim 1 , wherein the administering is once daily administration.
3. The method according to claim 1 , wherein the estetrol component is estetrol.
4. The method according to claim 3 , wherein the estetrol is anhydrous estetrol.
5. The method according to claim 1 , wherein the dosage unit consists of 5 to 90 wt. % of the granules.
6. The method according to claim 1 , wherein the granules have a volume weighted average size between 30 and 200 μm.
7. The method according to claim 1 , wherein the granules have a volume weighted average size between 40 and 150 μm.
8. The method according to claim 1 , wherein the C 4 -C 12 sugar alcohol is selected from mannitol, erythritol, isomalt and combinations thereof.
9. The method 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.
10. The method according to claim 9 , wherein the particles have 10-50 wt. % of disintegrating agent and 40-90 wt. % of C 4 -C 6 sugar alcohol.
11. The method according to claim 10 , wherein the disintegrating agent is selected from crospovidone, hydroxypropyl cellulose, croscarrnellose sodium, crystalline cellulose and combinations thereof.
12. The method according to claim 9 , wherein the C 4 -C 6 sugar alcohol is selected from mannitol, xylitol and combinations thereof.
13. The method according to claim 1 , wherein the pharmaceutically acceptable ingredient comprises progestogen present in an amount of 0.05-10 mg.