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 - Publisher Copyright:
© 2017
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 -
