Novel polymorphic forms of an antidiabetic agent: process for their preparation and a pharmaceutical composition containing them

A polymorphic Form-II of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 5
• which is characterized by the data described hereunder:
• DSC:
• Endotherms at 131° C., 166.24° C. and 178.96° C.
• Exotherm at 169.73° C.
• X-ray powder diffraction (2θ):
• 6.78, 11.5, 12.08, 16.44, 19.34, 22.30, 22.72, 24.40, 26.66
• Infrared absorption bands (cm−1):
• 3055, 1711, 1589, 1510, 1491, 1376, 1274, 1111, 1039, 810, 730, 543.

A polymorphic Form-III of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 6
• which is characterized by the data described hereunder:
• DSC:
• Exotherm at 168.00° C.
• Endotherm at 182.20° C. (onset at 171° C.),
• Small endotherms at 99.66° C., 164.38° C.
• X-ray powder diffraction (2θ):
• 6.80, 12.10, 15.84, 17.02, 19.40, 22.32, 22.68, 2438, 26.36,
• Infrared absorption bands (cm−1):
• 3061, 1710, 1588, 1510, 1491, 1379, 1273, 1110, 1040, 805, 739, and 543.

A polymorphic Form-IV of L-arginine salt of (2S) 3-(4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 7
• which is characterized by the data described hereunder:
• DSC:
• Small Exotherm at 171.80° C.
• Endotherms at 149.85° C., 185.60° C. (onset at 147.78° C.)
• Small Endotherm at 164.51° C.
• X-ray powder diffraction (2θ):
• 6.78, 12.66, 15.96, 16.54, 19.34, 22.78, 24.42, 26.70, 31.70,
• Infrared absorption bands (cm−1):
• 3056, 1711, 1589, 1493, 1381, 1274, 1242, 1101, 1060, 805, 743, and 543.7.

A polymorphic Form-V of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 8
• which is characterized by the data described hereunder:
• DSC:
• Small exotherm at 173.82° C.
• Endotherm at 185.95° C., (onset at 178.09° C.)
• Small endotherms at 119.81° C., 164.69° C., 172.44° C.
• X-ray powder diffraction (2θ):
• 6.76, 12.10, 15.96, 17.00, 18.50, 19.40, 22.38, 22.44, 24.44, 26.30,
• Infrared absorption bands (cm−1). 3266, 3055, 1711, 1589, 1510, 1492, 1379, 1274, 1175, 1111, 1040, 918, 819, 730, 676, 544.

A polymorphic Form-VI of L-arginine salt of (2S) 3-[4-[2-(Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 9
• which is characterized by the data described hereunder:
• DSC:
• Exotherm at 157.98° C.,
• Endotherms at 179.11° C. and 183.69° C. (onset at 157.98° C.),
• Small endotherm at 77.80° C.
• X-ray powder diffraction (2θ):
• No diffraction peaks due to its amorphous nature,
• Infrared absorption bands (cm−1):
• 3065, 1629,.1490, 1377, 1273, 1244, 1109, 1042, 805, 740, 539.

A polymorphic Form-VII of L-arginine salt of (2S) 3-[4-[2-phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 10
• which is characterized by the data described hereunder:
• DSC:
• Exotherm at 132.93° C.,
• Endotherms at 176.63° C. (onset at 169.06° C.) and 184.09° C.
• X-ray powder diffraction (2θ):
• No diffraction peaks due to its amorphous nature,
• Infrared absorption bands (cm−1):
• 3065, 1629, 1490, 1377, 1273, 1109, 1042, 740, 541.

A polymorphic Form-VIII of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 11
• which is characterized by the data described hereunder:
• DSC:
• Exotherm at 158.27° C.
• Endotherm at 178.12° C. (onset at 167.15 C.),
• Small Endotherm at 152.72° C.
• X-ray powder diffraction (2θ):
• 4.16, 11.02, 15.94, 19.50, 20.22, 22.22, 27.38,
• Infrared absorption bands (cm−1):
• 3151, 1629, 1490, 1378, 1272, 1244, 1104, 1041, 742, 549.

A polymorphic Form-IX of L-arginine salt of (2S) 3-(4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 12
• which is characterized by the data described hereunder:
• DSC:
• Endotherm at 176.67° C. (onset at 173.36° C.), (FIG. 21)
• X-ray powder diffraction (2θ):
• 8.20, 12.42, 16.66, 18.80, 19.44, 22.30, 23.08, 27.38, 28.48, 29:84, (FIG. 9)
• Infrared absorption bands (cm−1):
• 3066, 1588, 1489, 1376, 1273, 1243, 1110, 1043, 919, 805, 737, 543, (FIG. 33)

A polymorphic Form-X of L-arginine, salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 13
• which is characterized-by the data described hereunder:
• DSC:
• Endotherm at 184.53° C.,)
• Exotherm at, 162.67° C.
• X-ray powder diffraction (2θ):
• No diffraction peaks due to its amorphous nature,
• Infrared absorption bands (cm−1):
• 3413, 1630, 1511, 1491, 1377, 1273, 1244, 1176, 1108, 741.

A polymorphic Form-XI of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 14
• which is characterized by the data described hereunder:
• DSC:
• Endotherm at 184.40° C. (onset at 177.67° C.),
• X-ray powder diffraction (2θ):
• 7.38, 7.56, 11.90, 12.32, 14.80, 16.40, 19.58, 20.48, 22.34, 22.90, 23.54,
• Infrared absorption bands (cm−1):
• 3383, 2925, 1629, 1510, 1490, 1377, 1273, 1243, 1090, 1041, 739, 539.

A mixture of polymorphic Form I and X of L-arginine salt of (2S) 3-[4-[2-(phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, having the formula I,

• 15
• which is characterized by the following data:
• DSC:
• Endotherms at 181.28° C., 185.31° C., (onset at 173.54° C.)
• X-ray powder diffraction (2θ):
• 8.16, 12.40, 16.64, 18.78, 19.42, 22.34, 22.80. 23.08, 29.84,
• Infrared absorption bands (cm−1):
• 3247, 3066, 1708, 1587, 1510, 1489, 1375, 1273, 1244, 1178, 1111, 1043, 805, 737, 673, 543.