Orodispersible dosage unit containing an estetrol component

• US 10,660,903 B2
• Filed: 07/02/2018
• Issued: 05/26/2020
• Est. Priority Date: 06/18/2015
• Status: Active Grant

• Current Assignee: Estetra S.A. (Abbvie Incorporated)
• Original Assignee: Estetra SPRL
• Inventors: Jaspart, Severine Francine Isabelle, Platteeuw, Johannes Jan, Van Den Heuvel, Denny Johan Marijn
• Primary Examiner(s): Pallay, Michael B.
• Application Number:
  US16/025,719
• Publication Number:
  US 20190125759A1
• Time in Patent Office: 694 Days
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

An orodispersible solid pharmaceutical dosage unit having a weight between 30 and 1,000 mg is disclosed. The dosage unit comprises (a) 0.1-25 wt. % of estetrol particles containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof; and (b) 75-99.9 wt. % of one or more pharmaceutically acceptable excipients. The solid dosage unit comprises at least 100 μg of the estetrol component and can be obtained by a process that comprises compressing a dry blend of estetrol particles and one or more pharmaceutically acceptable excipients into a solid dosage unit. The solid dosage unit is easy to manufacture and suited for sublingual, buccal or sublabial administration.

Claims

1. A process of preparing an estetrol orodispersible solid pharmaceutical dosage unit having a weight between 30 and 1,000 mg, the dosage unit comprising:

(a) 0.1-25 wt. % of estetrol particles containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters, and combinations thereof; and

(b) 75-99.9 wt. % of one or more pharmaceutically acceptable excipients;

wherein the solid dosage unit contains at least 100 μ

g of the estetrol component and disintegrates within less than 5 minutes when subjected to disintegration testing in accordance with USP <

701>

(“

Disintegration”

) using water as the disintegration medium, the process comprising;

(i) providing estetrol particles having a volume median diameter between 2 μ

m to 50 μ

m and containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof;

(ii) mixing 1 part by weight of the estetrol particles with 2-1,000 parts by weight of one or more pharmaceutically acceptable excipients to obtain a dry blend; and

(iii) compressing the dry blend into a solid dosage unit.

2. The process according to claim 1, wherein the process does not comprise addition of liquid solvent during or after the combining of the estetrol particles and the one or more pharmaceutically acceptable excipients.

3. The process according to claim 1, wherein the solid dosage unit is formed by direct compression.

4. The process according to claim 1, wherein the dosage unit has a weight between 40 and 500 mg.

5. The process according to claim 1, wherein the dosage unit contains 0.5-25 wt. % of the estetrol component.

6. The process according to claim 1, wherein the dosage unit contains 0.3-100 mg of the estetrol component.

7. The process according to claim 1, wherein the estetrol component is estetrol.

8. The process according to claim 1, wherein the estetrol particles have a volume median diameter of 3-35 μ

m.

9. The process according to claim 1, wherein the dosage unit contains 50-99.5 wt. % of filler selected from maltose, fructose, sucrose, lactose, glucose, galactose, trehalose, xylitol, sorbitol, erythritol, maltitol, mannitol, isomalt, microcrystalline cellulose, calcium salts, and combinations of any thereof.

10. The process according to claim 1, wherein the dosage unit contains 30-99.5 wt. % of filler selected from lactose, xylitol, sorbitol, erythritol, mannitol, microcrystalline cellulose, and combinations of any thereof.

11. The process according to claim 1, wherein the dosage unit contains 30-90 wt. % of sugar alcohol selected from mannitol, xylitol, and combinations thereof.

12. The process according to claim 1, wherein the dosage unit contains 0.1-20 wt. % of a disintegrating agent selected from modified starches, crosslinked polyvinyl pyrrolidone, crosslinked carmellose, and combinations of any thereof.

13. The process according to claim 1, wherein the dosage unit contains 5-40 wt. % of microcrystalline cellulose.

14. The process according to claim 1, wherein the dosage unit contains 0.1-2 wt. % of lubricant selected from sodium stearyl fumarate, magnesium stearate, stearic acid, sodium lauryl sulfate, talc, polyethylene glycol, calcium stearate, and combinations of any thereof.