Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin

Jun Hui Deng; Tong Bu Lu; Changquan Calvin Sun; Jia Mei Chen

doi:10.1016/j.ejps.2017.04.008

Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin

Jun Hui Deng, Tong Bu Lu, Changquan Calvin Sun, Jia Mei Chen

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H₂O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H₂O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.

Original language	English (US)
Pages (from-to)	255-261
Number of pages	7
Journal	European Journal of Pharmaceutical Sciences
Volume	104
DOIs	https://doi.org/10.1016/j.ejps.2017.04.008
State	Published - Jun 15 2017

Bibliographical note

Funding Information:
This work was financially supported by NSFC (No. 21571194), NSF of Guangdong Province (No. S2012030006240), Guangdong special support plan for youth science and technology innovation talents (No. 2014TQ01R159) and National Key Scientific Instrument and Equipment Development Project (No. 2013YQ24051108). Jia-Mei Chen was supported by the China Scholarship Council for one year study at the University of Minnesota.

Publisher Copyright:
© 2017

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

Acetonitrile (PubChem CID: 6342)
Citric acid (PubChem CID: 311)
Dapagliflozin (PubChem CID: 9887712)
Dapagliflozin propanediol (PubChem CID: 24906252)
Isopropyl acetate (PubChem CID: 7915)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.ejps.2017.04.008

OpenUrl availability

Full text

Cite this

@article{c5931f4d6f81498b801faed41611a946,

title = "Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin",

abstract = "Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.",

keywords = "Acetonitrile (PubChem CID: 6342), Citric acid (PubChem CID: 311), Dapagliflozin (PubChem CID: 9887712), Dapagliflozin propanediol (PubChem CID: 24906252), Isopropyl acetate (PubChem CID: 7915)",

author = "Deng, {Jun Hui} and Lu, {Tong Bu} and Sun, {Changquan Calvin} and Chen, {Jia Mei}",

note = "Funding Information: This work was financially supported by NSFC (No. 21571194), NSF of Guangdong Province (No. S2012030006240), Guangdong special support plan for youth science and technology innovation talents (No. 2014TQ01R159) and National Key Scientific Instrument and Equipment Development Project (No. 2013YQ24051108). Jia-Mei Chen was supported by the China Scholarship Council for one year study at the University of Minnesota. Publisher Copyright: {\textcopyright} 2017 Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2017",

month = jun,

day = "15",

doi = "10.1016/j.ejps.2017.04.008",

language = "English (US)",

volume = "104",

pages = "255--261",

journal = "European Journal of Pharmaceutical Sciences",

issn = "0928-0987",

publisher = "Elsevier",

}

TY - JOUR

T1 - Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin

AU - Deng, Jun Hui

AU - Lu, Tong Bu

AU - Sun, Changquan Calvin

AU - Chen, Jia Mei

N1 - Funding Information: This work was financially supported by NSFC (No. 21571194), NSF of Guangdong Province (No. S2012030006240), Guangdong special support plan for youth science and technology innovation talents (No. 2014TQ01R159) and National Key Scientific Instrument and Equipment Development Project (No. 2013YQ24051108). Jia-Mei Chen was supported by the China Scholarship Council for one year study at the University of Minnesota. Publisher Copyright: © 2017 Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2017/6/15

Y1 - 2017/6/15

N2 - Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.

AB - Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.

KW - Acetonitrile (PubChem CID: 6342)

KW - Citric acid (PubChem CID: 311)

KW - Dapagliflozin (PubChem CID: 9887712)

KW - Dapagliflozin propanediol (PubChem CID: 24906252)

KW - Isopropyl acetate (PubChem CID: 7915)

UR - http://www.scopus.com/inward/record.url?scp=85018497454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018497454&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2017.04.008

DO - 10.1016/j.ejps.2017.04.008

M3 - Article

C2 - 28412482

AN - SCOPUS:85018497454

SN - 0928-0987

VL - 104

SP - 255

EP - 261

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

ER -

Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this