Showing posts with label WO 2016016774. Show all posts
Showing posts with label WO 2016016774. Show all posts

Sunday 7 February 2016

Canagliflozin , New patent, WO 2016016774, SUN PHARMACEUTICAL INDUSTRIES LIMITED

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WO2016016774, CRYSTALLINE FORMS OF CANAGLIFLOZIN
SUN PHARMACEUTICAL INDUSTRIES LIMITED [IN/IN]; Sun House, Plot No. 201 B/1 Western Express Highway Goregaon (E) Mumbai, Maharashtra 400 063 (IN)
SANTRA, Ramkinkar; (IN).
NAGDA, Devendra, Prakash; (IN).
THAIMATTAM, Ram; (IN).
ARYAN, Satish, Kumar; (IN).
SINGH, Tarun, Kumar; (IN).
PRASAD, Mohan; (IN).
GANGULY, Somenath; (IN).
WADHWA, Deepika; (IN)
The present invention relates to crystalline forms of canagliflozin, processes for their preparation, and their use for the treatment of type 2 diabetes mellitus. A crystalline Form R1of canagliflozin emihydrate. The crystalline Form R1 of canagliflozin hemihydrate of claim 1, characterized by an X-ray powder diffraction peaks having d-spacing values at about 3.1, 3.7, 4.6, and 8.9 A
The present invention relates to crystalline forms of canagliflozin, processes for their preparation, and their use for the treatment of type 2 diabetes mellitus.
Canagliflozin hemihydrate, chemically designated as (l<S)-l,5-anhydro-l-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Its chemical structure is represented by Formula I.
Formula I
U.S. Patent Nos. 7,943,582 and 8,513,202 disclose crystalline forms of canagliflozin hemihydrate.
PCT Publication No. WO 2009/035969 discloses a crystalline form of
canagliflozin, designated as I-S.
PCT Publication No. WO 2013/064909 discloses crystalline complexes of canagliflozin with L-proline, D-proline, and L-phenylalanine, and the processes for their preparation.
PCT Publication No. WO 2014/180872 discloses crystalline non-stoichiometric hydrates of canagliflozin (HxA and HxB), and the process for their preparation.
PCT Publication No. WO 2015/071761 discloses crystalline Forms B, C, and D of canagliflozin.
Chinese Publication Nos. CN 103980262, CN 103936726, CN 103936725, CN 103980261, CN 103641822, CN 104230907, CN 104447722, CN 104447721, and CN 104130246 disclose different crystalline polymorphs of canagliflozin.
In the pharmaceutical industry, there is a constant need to identify critical physicochemical parameters of a drug substance such as novel salts, polymorphic forms, and co-crystals, that affect the drug's performance, solubility, and stability, and which may play a key role in determining the drug's market acceptance and success.
The discovery of new forms of a drug substance may improve desirable processing properties of the drug, such as ease of handling, storage stability, and ease of purification. Accordingly, the present invention provides novel crystalline forms of canagliflozin having enhanced stability over known crystalline forms of canagliflozin.

EXAMPLES
Example 1 : Preparation of a crystalline Form Rl of canagliflozin hemihydrate
Amorphous canagliflozin (5 g) was suspended in an aqueous solution of sodium formate (80 mL of a solution prepared by dissolving 137.7 g of sodium formate in 180 mL of de-ionized water). The suspension was stirred at room temperature for 20 hours to obtain a reaction mixture. De-ionized water (100 mL) was added to the reaction mixture, and then the reaction mixture was stirred for 1.5 hours. De-ionized water (50 mL) was added to the reaction mixture, and then the reaction mixture was stirred for 30 minutes. The reaction mixture was filtered, then washed with de-ionized water (300 mL), and then dried under vacuum for 12 hours to obtain a solid. The solid was further dried under vacuum at 60°C for 6 hours.
Yield: 4.71 g
Example 2: Preparation of a crystalline Form R2 of canagliflozin monohydrate
Amorphous canagliflozin (5 g) was suspended in an aqueous solution of sodium formate (80 mL of a solution prepared by dissolving 137.7 g of sodium formate in 180 mL of de-ionized water). The suspension was stirred at room temperature for 20 hours to obtain a reaction mixture. De-ionized water (100 mL) was added to the reaction mixture, and then the reaction mixture was stirred for 1.5 hours. De-ionized water (50 mL) was added to the reaction mixture, and then the reaction mixture was stirred for 30 minutes. The reaction mixture was filtered, then washed with de-ionized water (300 mL), and then dried under vacuum for 12 hours at room temperature.
Yield: 4.71 g
Example 3 : Preparation of a crystalline Form R2 of canagliflozin monohydrate
Canagliflozin hemihydrate (0.15 g; Form Rl obtained as per Example 1) was suspended in de-ionized water (3 mL). The suspension was stirred at room temperature for 24 hours. The reaction mixture was filtered, then dried at room temperature under vacuum for 5 hours.
Yield: 0.143 g
Example 4: Preparation of a crystalline Form R3 of canagliflozin hydrate
Amorphous canagliflozin (100 g) was suspended in an aqueous solution of sodium formate (1224 g of sodium formate in 1600 mL of de-ionized water). The suspension was stirred at room temperature for 20 hours to obtain a reaction mixture. De-ionized water
(2000 mL) was added to the reaction mixture, and then the reaction mixture was stirred for one hour. De-ionized water (1000 mL) was added to the reaction mixture, and then the reaction mixture was stirred for another one hour. The reaction mixture was filtered, then washed with de-ionized water (6000 mL), and then dried under vacuum for 30 minutes to obtain a solid. The solid was then dried under vacuum at 30°C to 35°C until a water content of 8% to 16% was attained.
Yield: 100 g
Sun Pharma's Dilip Shanghvi has become the stuff of legends
 
From top left: Abhay Gandhi (CEO-India Business-Sun Pharma), Kal Sundaram (CEO-TARO). Middle row (L-R): Israel Makov (chairman, Sun Pharma), Dilip Shanghvi (Founder and MD, Sun Pharma) Uday Baldota (CFO, Sun Pharma). Bottom: Kirti Ganorkar (Senior VP, Business development, Sun Pharma)

./////////////Canagliflozin , New patent, WO 2016016774, SUN PHARMACEUTICAL INDUSTRIES LIMITED