ESTRIOL FORMULATIONS

• US 20110250274A1
• Filed: 09/18/2009
• Published: 10/13/2011
• Est. Priority Date: 09/19/2008
• Status: Abandoned Application

• Current Assignee: Evestra, Inc.
• Original Assignee: Evestra, Inc.
• Inventors: Elger, Walter, Nickisch, Klaus, Shaked, Ze'ev
• Application Number:
  US13/063,803
• Publication Number:
  US 20110250274A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

Disclosed herein are oral dosage forms and methods of their use, in particular oral dosage systems for the delivery of estriol compounds. Embodiments described herein relate to rapidly disintegrating oral dosage formulations that disintegrate in the saliva of the buccal and/or sublingual and/or esophageal cavity. Oral dosage forms described herein relate to stabilized amorphous and nanocrystalline forms of the active ingredients of the formulations.

Claims

1. An oral dosage form comprising an estriol compound and a pharmaceutically acceptable matrix material, wherein the oral dosage form releases at least about 90% of the estriol compound in a time of less than about 300 seconds when contacted with saliva of the buccal and/or sublingual cavity.

2. The oral dosage form of claim 1, wherein the oral dosage form comprises about 0.01 mg to about 2 mg of the estriol compound.

3. The oral dosage form of claim 1, wherein at least a portion of the estriol compound is in a stabilized amorphous form.

4. The oral dosage form of claim 1, wherein at least a portion of the estriol compound is in a stabilized nanocrystalline form.

5. The oral dosage form of claim 1, wherein the pharmaceutically acceptable matrix material comprises a polyethylene glycol polymer.

6. The oral dosage form of claim 1, wherein the pharmaceutically acceptable matrix material comprises a cellulose based matrix material.

7. The oral dosage form of claim 1, wherein the pharmaceutically acceptable matrix material comprises a vinyl based matrix material.

8. The oral dosage form of claim 1, wherein the pharmaceutically acceptable matrix material comprises a polyvinyl pyrrolidone polymer.

9. The oral dosage form of claim 1, wherein the pharmaceutically acceptable matrix material comprises an acrylic acid-based polymer, a methacrylic acid-based polymer, an acrylic acid—

methacrylic acid based copolymer, or a mixture thereof.

10. The oral dosage form of claim 1, further comprising a filler.

11. The oral dosage form of claim 1, further comprising a taste enhancing agent.

12. The oral dosage form of claim 1, further comprising a disintegrant.

13. The oral dosage form of claim 1, further comprising a stabilizer.

14. The oral dosage form of claim 1, further comprising one or more poloxamers.

15. The oral dosage form of claim 1, further comprising a mucoadhesive/bioadhesive polymer.

16. The oral dosage from of claim 1, wherein the oral dosage form is in the form of a tablet.

17. The oral dosage form of claim 1, wherein the oral dosage form has a thickness of less than 5000 microns.

18. The oral dosage form of claim 1, wherein the oral dosage form comprises:

a first layer, wherein the first layer comprises the estriol compound and the pharmaceutically acceptable matrix material, and wherein the first layer releases at least about 90% of the estriol compound in a time of less than about 300 seconds when contacted with saliva of the buccal and/or sublingual cavity; and

a second layer that includes an estriol compound and a pharmaceutically acceptable matrix material, wherein the second layer releases between about 10% and 50% of the estriol compound contained therein after 30 minutes of contact with the saliva of the buccal and/or sublingual cavity, and at least about 90% of the estriol compound in a time of less than about 4 hours when contacted with saliva of the buccal and/or sublingual cavity.

19. The oral dosage form of claim 1, wherein the oral dosage form comprises:

a first layer, wherein the first layer comprises the estriol compound and the pharmaceutically acceptable matrix material, and wherein the first layer releases at least about 90% of the estriol compound in a time of less than about 300 seconds when contacted with saliva of the buccal and/or sublingual cavity; and

a second layer that includes an estrogen compound and a pharmaceutically acceptable matrix material, wherein the second layer releases between about 10% and 50% of the estrogen compound contained therein after 30 minutes of contact with the saliva of the buccal and/or sublingual cavity, and at least about 90% of the estrogen compound in a time of less than about 4 hours when contacted with saliva of the buccal and/or sublingual cavity.

20. The oral dosage form of claim 1, wherein the oral dosage form comprises:

a first layer, wherein the first layer comprises the estriol compound and the pharmaceutically acceptable matrix material, and wherein the first layer releases at least about 90% of the estriol compound in a time of less than about 300 seconds when contacted with saliva of the buccal and/or sublingual cavity; and

a second layer that includes a progestogen compound and a pharmaceutically acceptable matrix material, wherein the second layer releases between about 10% and 50% of the progestogen compound contained therein after 30 minutes of contact with the saliva of the buccal and/or sublingual cavity, and at least about 90% of the progestogen compound in a time of less than about 4 hours when contacted with saliva of the buccal and/or sublingual cavity.

21. A method of treating perimenopausal conditions in a subject comprising orally administering to a subject an oral dosage form comprising an effective amount of an estriol compound, and a pharmaceutically acceptable matrix material, wherein the oral dosage form releases at least about 90% of the estriol in a time of less than about 300 seconds when contacted with saliva of the buccal and/or sublingual cavity of the subject.

22-84. -84. (canceled)