New Cocrystals of Ligustrazine: Enhancing Hygroscopicity and Stability

Yifei Xie; Lixiang Gong; Yue Tao; Baoxi Zhang; Li Zhang; Shiying Yang; Dezhi Yang; Yang Lu; Guanhua Du

doi:10.3390/molecules29102208

Molecules (May 2024)

New Cocrystals of Ligustrazine: Enhancing Hygroscopicity and Stability

Yifei Xie,
Lixiang Gong,
Yue Tao,
Baoxi Zhang,
Li Zhang,
Shiying Yang,
Dezhi Yang,
Yang Lu,
Guanhua Du

Affiliations

Yifei Xie: Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Lixiang Gong: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Yue Tao: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Baoxi Zhang: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Li Zhang: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Shiying Yang: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Dezhi Yang: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Yang Lu: Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China
Guanhua Du: Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China

DOI: https://doi.org/10.3390/molecules29102208
Journal volume & issue: Vol. 29, no. 10
p. 2208

Abstract

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Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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