Dapagliflozin crystalline form and preparation method thereof

Patent metadata

Field	Value
Publication number	US-2016347731-A1
Application number	US-201515117533-A
Country	US
Kind code	A1
Filing date	Jan 19, 2015
Priority date	Feb 10, 2014
Publication date	Dec 1, 2016
Grant date	—

Abstract

A crystalline form of dapagliflozin represented by formula (I) is provided. The crystalline form has a characteristic absorption peak in an X-ray powder diffraction pattern at a diffraction angle 2θ and interplanar spacing (value d) at about 4.318 (20.45) in an X-ray powder diffraction pattern. The crystalline form can be prepared by dissolving dapagliflozin in good organic solvents, adding poor solvents, stirring to crystallization, filtering and drying. The provided crystalline form of dapagliflozin has the following features: good solubility, low hygroscopicity, high stability and good preparation reproducibility.

First claim

1 . A crystalline form of dapagliflozin represented by formula (I):

the crystalline form having a characteristic X-ray powder diffraction (XRPD) peak at:
Angle (2θ) d-Value (Angstrom)
about 4.318 about 20.45.

2 . A method for preparing the crystalline form of dapagliflozin represented by formula (I) according to claim 1 , wherein the crystalline form of dapagliflozin is obtained in an organic solvent at a temperature of 0° C. to 30° C.

3 . The method according to claim 2 , wherein the method comprises:
(a) dissolving dapagliflozin in a good organic solvent; (b) adding a poor solvent to the solution of dapagliflozin in the good solvent obtained in step (a), thereby producing a mixture; (c) stirring the mixture to crystallization; (d) filtering the precipitate from the mixture; and (e) drying the filtered precipitate obtained in step (d) at a temperature of 0 to 30° C. to obtain the crystalline form.

4 . The method according to claim 3 , wherein the good organic solvent is selected from the group consisting of ether solvents.

5 . The method according to claim 3 , wherein the poor solvent is selected from the group consisting of alkane solvents.

6 . The method according to claim 2 , wherein the temperature is in a range of 10 to 20° C.

7 . The method according to claim 3 , wherein the mixture is stirred to crystallization in step (c) for a duration of 1.5 to 2 hours.

8 . The method according to claim 3 , wherein the filtered precipitate is dried at a temperature in a range of 10 to 30° C.

9 . The method according to claim 3 , wherein the drying is under vacuum.

10 . The crystalline form of dapagliflozin according to claim 1 , having a XRPD pattern as shown in FIG. 1 .

11 . The method according to claim 4 , wherein the good organic solvent is diethyl ether or methyl t-butyl ether.

12 . The method according to claim 5 , wherein the alkane solvent is n-hexane or n-heptane.

Assignees

• Jiangsu Hansoh Pharmaceutical Group Co Ltd

Inventors

• Zhu Xifeng
• Li Xiaobi
• Zhang Tiancheng
• Yuan Fuping

Classifications

• A61K31/70

  Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) · CPC title

• C07H7/04

  Carbocyclic radicals · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07H1/06

  Separation; Purification · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title