PHARMACEUTICAL FORMULATION OF PALBOCICLIB AND A PREPARATION METHOD THEREOF

• US 20170281631A1
• Filed: 06/05/2017
• Published: 10/05/2017
• Est. Priority Date: 03/29/2016
• Status: Active Grant

• Current Assignee: Shenzhen Pharmacin Co., Ltd.
• Original Assignee: Shenzhen HLK Pharmaceuticals Co., Ltd.
• Inventors: WANG, Zeren, XU, Jun, QU, Long
• Granted Patent: US 10,449,195 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention belongs to the pharmaceutical field, and in particular, it relates to a pharmaceutical formulation of palbociclib and a preparation method thereof. The pharmaceutical formulation comprises palbociclib, an acidic auxiliary material, and optionally a hydrophilic high-molecular material, which has better solubility and in vitro dissolution property as compared with the conventional formulation and can be used for enhancing in vivo absorption and bioavailability of palbociclib.

Claims

1. A pharmaceutical formulation of palbociclib, comprising a palbociclib free base or a pharmaceutically acceptable salt thereof and an acidic auxiliary material, wherein the acidic auxiliary material is one or more selected from the group consisting of tartaric acid, fumaric acid, succinic acid, citric acid, lactic acid and malic acid, and wherein a mass ratio of the acidic auxiliary material to palbociclib is from 0.2:

1 to 5;

1.

2. The pharmaceutical formulation according to claim 1, wherein the palbociclib free base or the salt thereof is a solid and has a particle size of 20 μ

m or less.

3. The pharmaceutical formulation according to claim 1, wherein the mass ratio of the acidic auxiliary material to palbociclib is from 0.5:

1 to 2;

1.

4. The pharmaceutical formulation according to claim 1, which is a tablet or capsule.

5. The pharmaceutical formulation according to claim 4, wherein the tablet or capsule has a dosage of from 25 mg to 500 mg.

6. The pharmaceutical formulation according to claim 5, wherein the tablet or capsule has a dosage of from 50 mg to 150 mg.

14. A method for the preparation of a pharmaceutical formulation according to claim 1, comprising:

mixing an API of palbociclib with a pharmaceutically acceptable acidic auxiliary material;

or pulverizing the API of palbociclib to control the particle size at 20 μ

m or less, and then mixing with the acidic auxiliary material;

or adding the acidic auxiliary material to the API, mixing and co-pulverizing to control the particle size at 20 μ

m or less.

17. Use of a pharmaceutical formulation according to claim 1 in the manufacture of a medicament for the treatment of breast cancer.

7. A solid dispersion of palbociclib, comprising a palbociclib free base or a pharmaceutically acceptable salt thereof, an acidic auxiliary material and a hydrophilic high-molecular material.

8. The solid dispersion according to claim 7, wherein the acidic auxiliary material is selected from one or more pharmaceutically acceptable organic acids and optionally one or more pharmaceutically acceptable inorganic acids.

9. The solid dispersion according to claim 8, wherein the pharmaceutically acceptable organic acid is selected from the group consisting of tartaric acid, fumaric acid, succinic acid, citric acid, lactic acid, malic acid, aliphatic sulfonic acid and aromatic sulfonic acid, and the pharmaceutically acceptable inorganic acid is selected from the group consisting of hydrochloric acid, sulfuric acid and phosphoric acid.

10. The solid dispersion according to claim 9, wherein the aliphatic sulfonic acid is selected from the group consisting of methanesulfonic acid, ethanesulfonic acid and isethionic acid, and the aromatic sulfonic acid is selected from the group consisting of benzenesulfonic acid and p-toluenesulfonic acid.

11. The solid dispersion according to claim 7, wherein the hydrophilic high-molecular material is one or more selected from the group consisting of povidone K30, copovidone VA64, Soluplus, hydroxypropylmethylcellulose E5, hydroxypropylmethylcellulose acetate succinate, hydroxypropyl-β

-cyclodextrin and sulfobutyl ether-β

-cyclodextrin.

12. The solid dispersion according to claim 7, wherein the mass ratio of the hydrophilic high-molecular material to palbociclib is from 0.1:

1 to 10;

1, and the mass ratio of the acidic auxiliary material to palbociclib is from 0.2;

1 to 5;

1.

13. The solid dispersion according to claim 12, wherein the mass ratio of the hydrophilic high-molecular material to palbociclib is from 1:

1 to 3;

1, and the mass ratio of the acidic auxiliary material to palbociclib is from 0.5;

1 to 2;

1.

15. A method for the preparation of a solid dispersion according to claim 7, comprising:

mixing an API of palbociclib with an acidic auxiliary material, adding a solvent for dissolving or dispersing, adding a hydrophilic high-molecular material, dissolving or dispersing evenly, and removing the solvent by heating.

16. The method for the preparation according to claim 15, wherein the concentration of the API of palbociclib in the solvent is up to 50 mg/ml or more.