PHARMACEUTICAL COMPOSITIONS COMPRISING BORONIC ACID COMPOUNDS

• US 20110178470A1
• Filed: 03/31/2011
• Published: 07/21/2011
• Est. Priority Date: 10/01/2008
• Status: Abandoned Application

• Current Assignee: Dr. Reddy's Lab., Inc. (Dr. Reddy's Laboratories Ltd.), Dr. Reddy's Laboratories Ltd.
• Original Assignee: Dr. Reddy's Lab., Inc. (Dr. Reddy's Laboratories Ltd.), Dr. Reddy's Laboratories Ltd.
• Inventors: Shantreddy, Soogareddy Channareddy, Chhagan, Wagh Sanjay, Sridhar, Mittapally, Sreedhar, Bandari, Kovoru, Krishnam Raju, Chandrkanth, Keni Devendra, Kranthikumar, Hinge, Nallamothu, Lavanya, Sukumar, Pillai Raviraj, Banda, Nagaraju, Kocherlakota, Chandrasekhar
• Application Number:
  US13/076,839
• Publication Number:
  US 20110178470A1
• Time in Patent Office: Days
• US Class Current: 604/187
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Pharmaceutical compositions comprising bortezomib for oral or parenteral administration. Specific aspects relate to stable, sugar free pharmaceutical compositions of bortezomib, including its pharmaceutically acceptable salts or solvates, in the form of ready-to-use solutions, lyophilized forms, or physical admixtures, and the preparation thereof. Other aspects include processes for preparing compositions and methods of using compositions for treating various types of cancers in mammals.

Claims

1. A pharmaceutical formulation in a liquid state, comprising bortezomib or a pharmaceutically acceptable salt thereof and at least one organic solvent.

2. The pharmaceutical formulation of claim 1, wherein an organic solvent comprises an alcohol, N,N-dimethylacetamide, dimethylisosorbide, dimethylsulfoxide, N-methylpyrrolidone, or a combination of any two or more thereof.

3. The pharmaceutical formulation of claim 1, further comprising water.

4. The pharmaceutical formulation of claim 1, wherein an organic solvent is a primary, secondary, or tertiary alcohol.

5. The pharmaceutical formulation of claim 1, comprising from about 1 to about 100 percent by volume of organic solvent.

6. The pharmaceutical formulation of claim 1, further comprising one or more of pharmaceutically acceptable solubilizers and stabilizers.

7. The pharmaceutical formulation of claim 1, the form of a ready-to-use solution.

8. The pharmaceutical formulation of claim 1, packaged in a glass vial, plastic vial, or pre-filled syringe.

9. A solid pharmaceutical formulation, comprising a liquid of claim 1 after being lyophilized to form a solid.

10. A sugar free pharmaceutical formulation, comprising bortezomib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. The pharmaceutical formulation of claim 10, wherein a pharmaceutically acceptable carrier comprises at least one of an amino acid, a vitamin, a carboxylic acid, and sodium chloride.

12. The pharmaceutical formulation of claim 10, wherein a pharmaceutically acceptable carrier further comprises a stabilizing agent.

13. The pharmaceutical formulation of claim 10, further comprising ethylenediaminetetraacetic acid or a salt thereof.

14. The pharmaceutical formulation of claim 10, wherein bortezomib and a pharmaceutical carrier are present in molar ratios ranging from about 0.5:

1 to about 100;

1.

15. The pharmaceutical formulation of claim 10, in the form of a ready-to-use solution, a lyophilized solid, or a solid physical admixture.

16. The pharmaceutical formulation of claim 10, further comprising a pH adjusting agent.

17. A pharmaceutical formulation, comprising bortezomib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier comprising at least one of cyclodextrin and a solubilizer.

18. The pharmaceutical formulation of claim 17, wherein a cyclodextrin comprises an alpha-, beta-, or gamma-cyclodextrin, or a derivative thereof.

19. The pharmaceutical formulation of claim 17, wherein a solubilizer comprises at least one of a surface active agent, a co-solvent, and a complexing agent.

20. The pharmaceutical formulation of claim 17, wherein bortezomib and a pharmaceutically acceptable carrier are present in a molar ratio ranging from about 0.5:

1 to about 100;

1.

21. The pharmaceutical formulation of claim 17, in a solid form for oral administration.

22. The pharmaceutical formulation of claim 17, in lyophilized form or a physical admixture, for reconstitution with a liquid.

23. A solid pharmaceutical formulation, prepared by lyophilizing a solution comprising bortezomib and an alcohol.

24. The solid pharmaceutical formulation of claim 23, wherein an alcohol comprises t-butyl alcohol.

25. The solid pharmaceutical formulation of claim 23, wherein a solution consists essentially of bortezomib and t-butyl alcohol.