Cocrystal of Dapagliflozin with Citric Acid: Enhanced Hygroscopic and Thermal Stability
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- 英文论文题名：Cocrystal of Dapagliflozin with Citric Acid: Enhanced Hygroscopic and Thermal Stability
- 论文作者：Jun-Hui Deng ; Jia-Mei Chen ; Tong-Bu Lu
- 英文论文作者：Jun-Hui Deng ; Jia-Mei Chen ; Tong-Bu Lu ; School of Pharmaceutical Sciences ; Sun Yat-Sen University ; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry ; School of Chemistry and Chemical Engineering ; Sun Yat-Sen University
- 年：2016
- 作者机构：School of Pharmaceutical Sciences,Sun Yat-Sen University;MOE Key Laboratory of Bioinorganic and Synthetic Chemistry,School of Chemistry and Chemical Engineering,Sun Yat-Sen University;
- 会议召开时间：2016-12-19
- 会议录名称：中国晶体学会第六届学术年会暨会员代表大会（第六届全国晶型药物研发技术学术研讨会）论文摘要集
- 英文会议录名称：Abstracts of the 6th Annual Conference of Chinese Crystallographic Society
- 语种：英文
- 分类号：R943
- 学会代码：ZGJY
- 会议名称：中国晶体学会第六届学术年会暨会员代表大会——第六届全国晶型药物研发技术学术研讨会
- 会议地点：中国广东广州
- 主办单位：中国晶体学会
- 学会名称：中国晶体学会
- 页数：1
- 文件大小：185k
- 原文格式：D
- 会议级别：全国
摘要
Dapagliflozin(DAP) is a potent and selective sodium-glucose contransporter-2(SGLT-2) inhibitor, and performed as an efficacious treatment for type 2 diabetes. Sever hygroscopicity of DAP hinder the usage of its free form during process of pharmaceutical production. A solvate form(dapagliflozin propanediol, DAP-PDO-H_2O) is used in the market, which, however, also faces problem of thermal instability as higher vapor pressure of solvent molecules in crystal lattice. The present study obtained a new cocrystal of DAP with citric acid(DAP-CA). DAP-CA cocrystal was identified and characterized by ~1H nuclear magnetic resonance(~1H-NMR), Fourier transform infra-red spectroscopy(FTIR), powder X-ray diffraction(PXRD) and thermal analysis, It was also evaluated by dynamic vapor sorption(DVS) and accelerated stability test under 40 ℃/75% RH, as well as powder dissolution test. DAP-CA cocrystal showed enhanced stability against both humidity and high temperature compared to the market form without compromising the dissolution solubility.
Dapagliflozin(DAP) is a potent and selective sodium-glucose contransporter-2(SGLT-2) inhibitor, and performed as an efficacious treatment for type 2 diabetes. Sever hygroscopicity of DAP hinder the usage of its free form during process of pharmaceutical production. A solvate form(dapagliflozin propanediol, DAP-PDO-H_2O) is used in the market, which, however, also faces problem of thermal instability as higher vapor pressure of solvent molecules in crystal lattice. The present study obtained a new cocrystal of DAP with citric acid(DAP-CA). DAP-CA cocrystal was identified and characterized by ~1H nuclear magnetic resonance(~1H-NMR), Fourier transform infra-red spectroscopy(FTIR), powder X-ray diffraction(PXRD) and thermal analysis, It was also evaluated by dynamic vapor sorption(DVS) and accelerated stability test under 40 ℃/75% RH, as well as powder dissolution test. DAP-CA cocrystal showed enhanced stability against both humidity and high temperature compared to the market form without compromising the dissolution solubility.
Dapagliflozin(DAP) is a potent and selective sodium-glucose contransporter-2(SGLT-2) inhibitor, and performed as an efficacious treatment for type 2 diabetes. Sever hygroscopicity of DAP hinder the usage of its free form during process of pharmaceutical production. A solvate form(dapagliflozin propanediol, DAP-PDO-H_2O) is used in the market, which, however, also faces problem of thermal instability as higher vapor pressure of solvent molecules in crystal lattice. The present study obtained a new cocrystal of DAP with citric acid(DAP-CA). DAP-CA cocrystal was identified and characterized by ~1H nuclear magnetic resonance(~1H-NMR), Fourier transform infra-red spectroscopy(FTIR), powder X-ray diffraction(PXRD) and thermal analysis, It was also evaluated by dynamic vapor sorption(DVS) and accelerated stability test under 40 ℃/75% RH, as well as powder dissolution test. DAP-CA cocrystal showed enhanced stability against both humidity and high temperature compared to the market form without compromising the dissolution solubility.
引文
[1]Chen,J.M.,Wang,Z.Z.,Wu,C.B.,et al.Crystal engineering approach to improve the solubility of mebendazole,Cryst Eng Comm.2012,14,6221-6229.
[2]Desiraju G.R.,Crystal Engineering:From Molecule to Crystal,J.Am.Chem.Soc.2013,135,9952-9967.
[3]Wang Z.Z.,Chen J.M.,Lu T.B.,Enhancing the Hygroscopic Stability of S-Oxiracetam via Pharmaceutical Cocrystals.Cryst.Growth Des.2012,12,4562-4566
[2]Desiraju G.R.,Crystal Engineering:From Molecule to Crystal,J.Am.Chem.Soc.2013,135,9952-9967.
[3]Wang Z.Z.,Chen J.M.,Lu T.B.,Enhancing the Hygroscopic Stability of S-Oxiracetam via Pharmaceutical Cocrystals.Cryst.Growth Des.2012,12,4562-4566