PHARMACEUTICAL COMPOSITION

• US 20110275597A1
• Filed: 01/08/2010
• Published: 11/10/2011
• Est. Priority Date: 01/09/2009
• Status: Active Grant

• Current Assignee: Sun Pharma Advanced Research Company Limited (Shanghvi Finance Pvt Ltd.)
• Original Assignee: Sun Pharma Advanced Research Company Limited (Shanghvi Finance Pvt Ltd.)
• Inventors: Subramanian, N., Namdeo, Alok B., Bhowmick, Subhas Balaram
• Granted Patent: US 9,095,514 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/133 having hydroxy groups, e.g. sphingosine
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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

The present invention relates to a parenteral pharmaceutical composition comprising therapeutically effective amounts of N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the composition is stable.

Claims

1. A parenteral pharmaceutical composition comprising therapeutically effective amounts of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the composition is stable.

2. A parenteral pharmaceutical composition claimed in claim 1 wherein the pH of the composition is adjusted in the range of 6.8 to 8.2.

3. A parenteral pharmaceutical composition claimed in claim 2 wherein the pH of the composition is adjusted to a pH of about 7.0.

4. A parenteral pharmaceutical composition claimed in claim 3 wherein composition when in dry form shows the total impurities less than 0.68 at 1 month storage at 40°

C. and 75% relative humidity and upon reconstitution, the composition in solution form remains stable for at least 12 hours.

5. A parenteral pharmaceutical composition claimed in claim 2 wherein composition is in the dry form.

6. A parenteral pharmaceutical composition as claimed in claim 5 wherein composition is in the freeze dried form and remains stable at ambient conditions for six months.

7. A parenteral composition claimed in claim 1 wherein the molar ratio of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid and tromethamine is about 1:

3.

8. A parenteral composition claimed in claim 1 wherein the composition comprises a bulking agent selected from the group consisting of potassium chloride, sodium chloride, mannitol, lactose, sucrose, maltose, trehalose and mixtures thereof.

9. A method for formulating a N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid, said the method comprising:

(a) preparing an aqueous mixture comprising

(i) a N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid

(ii) tromethamine and a optionally a bulking agent and

(b) adjusting the pH of the solution to a pH of about 6.8 to 8.2 and

(c) lyophilizing the solution of (b).

10. A method claimed in claim 9 wherein the aqueous mixture further comprises water-miscible co-solvents.

11. A method claimed in claim 10 wherein the pH is adjusted in the range of about 6.9 to 7.2 by addition of an acid.