Pharmaceutical Formulations

• US 20140309250A1
• Filed: 11/21/2012
• Published: 10/16/2014
• Est. Priority Date: 11/23/2011
• Status: Active Grant

• Current Assignee: Array Biopharma Incorporated (Pfizer Inc.)
• Original Assignee: Novartis Ag
• Inventors: Verma, Daya, Li, Ping, Singh, Rajinder, Krishnamachan, Yogita, Shen, Xiaohong, Lee, Hanchen, Tan, LayChoo
• Granted Patent: US 9,387,208 B2
• Time in Patent Office: Days
• US Class Current: 514/275
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention relates to solid oral pharmaceutical formulations of (S)-methyl (1-((4-(3-(5-chloro-2-fluoro-3-(methylsulfonamido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamate (COMPOUND A) and the use of the formulations for treating proliferative diseases, such as solid tumor diseases.

Claims

1. A solid oral pharmaceutical formulation which comprises a solid dispersion comprising COMPOUND A.

2. A solid oral pharmaceutical formulation of claim 1, which comprises:

an inner phase which is a solid dispersion comprising COMPOUND A, and an external phase which comprises additional excipients.

3. A solid oral pharmaceutical formulation of claim 2 wherein the internal phase or the external phase comprises an acidifier.

4. The present invention further relates to a solid oral pharmaceutical formulation of claim 2, which comprises:

an inner phase which is a solid dispersion comprising COMPOUND A, a hydrophilic binder and a surfactant; and

an external phase which comprises additional excipients.

5. A solid oral pharmaceutical formulation of claim 1, which comprises:

an inner phase which is a solid dispersion comprising COMPOUND A, a hydrophilic binder, a surfactant and

an external phase which comprises one or more of an acidifier, a filler, a disintegrant, a flow enhancer and a lubricant.

6. Use of a solid oral pharmaceutical formulation of claim 1 for the preparation of a medicament for the treatment of a proliferative disease.

7. A method of treating a proliferative disease which comprises administering to a patient in need of treatment a therapeutically effective amount of a formulation according to claim 1.

8. Use of the solid oral formulations according to claim 1 for the treatment of a disease which responds to inhibition of B-RAF.

9. Use according to claim 8 wherein the disease is characterized by a mutation in B-RAF.

10. Use according to claim 9 wherein the disease is melanoma or colorectal cancer.