Granted Patent B2

US 12,427,114 · App. 18/621,501 · Granted Sep 30, 2025

Inventors: Séverine Francine Isabelle Jaspart (Bois-et-Borsu, BE); Johannes Jan Platteeuw (Boxtel, NL); Denny Johan Marijn Van Den Heuvel (Beuningen, NL)

Assignee: ESTETRA SRL

A61K9/2095A61K9/0056A61K9/2027A61K9/2054A61K9/2059A61K9/2077A61K31/565A61P5/00A61P15/18A61K9/1623

Abstract

Claims (20)

1. Dry estetrol-containing granules comprising:

70-95 wt. % of one or more granulation excipients; and

5-30 wt. % of estetrol particles having a volume median diameter of 2 μm to 50 μm and containing at least 90 wt. % of an estetrol component.

2. The dry estetrol-containing granules of claim 1 , obtained by a process comprising:

mixing the estetrol particles estetrol particles having a volume median diameter of 2 μm to 50 μm and containing at least 90 wt. % of the estetrol component with the one or more granulation excipients to produce a granulation mixture;

mixing the granulation mixture with a granulation liquid comprising at least 60 wt. % of a liquid solvent to produce estetrol-containing granules; and

removing liquid solvent from the estetrol-containing granules to produce said dry estetrol-containing granules.

3. The dry estetrol-containing granules of claim 1 , wherein the estetrol component is estetrol monohydrate.

4. A solid pharmaceutical dosage form comprising the dry estetrol-containing granules of claim 1 , wherein the solid pharmaceutical dosage form releases at least 50% of the estetrol component after 5 minutes in an aqueous dissolution medium.

5. The solid pharmaceutical dosage form of claim 4 , comprising from 1 mg to 20 mg of the estetrol component.

6. The solid pharmaceutical dosage form of claim 4 , comprising 20 mg of the estetrol component.

7. The solid pharmaceutical dosage form of claim 4 , further comprising a further pharmaceutically acceptable ingredient selected from progesterone, desogestrel, etonogestrel, gestodene, dienogest, levonorgestrel, norgestimate, norethisterone, norethisteron-acetate (NETA), nomegestrol, nomegestrol-acetate (NOMAC), drospirenone, trimegestone, nestorone, and dydrogesterone.

8. The solid pharmaceutical dosage form of claim 5 , further comprising 0.05-10 mg of drospirenone.

9. The solid pharmaceutical dosage form of claim 4 , wherein the dosage form is an orodispersible dosage form.

10. The solid pharmaceutical dosage form of claim 4 , wherein the estetrol particles are present in the dosage form in an amount of 0.5-25 wt. %.

11. The solid pharmaceutical dosage form of claim 4 , wherein the dosage form comprises a water-soluble carbohydrate selected from maltose, fructose, sucrose, lactose, glucose, galactose, trehalose, xylitol, sorbitol, erythritol, maltitol, mannitol, isomalt, and combinations thereof.

12. The solid pharmaceutical dosage form according to claim 4 , wherein the dosage form comprises 0.1-20 wt. % of a disintegrating agent selected from modified starches, crosslinked polyvinylpyrrolidone, crosslinked carmellose, and combinations thereof.

13. A female hormone replacement therapy method, comprising administering dry estetrol-containing granules of claim 1 to a subject in need thereof.

14. The method of claim 13 , comprising once daily administration of the granules during a period of at least 1 week.

15. A female contraception method, comprising administering dry estetrol-containing granules of claim 1 to a subject in need thereof.

Assignments (3)

Priority Claims (1)

Continuity (3)

References Cited (240)