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Crystal forms of a new 5-HT4 receptor agonist DA-6886

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Abstract

DA-6886 is a new 5-HT4 receptor agonist under development for the treatment of constipation-predominant irritable bowel syndrome. The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of DA-6886. Five crystal forms of DA-6886 have been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, and powder X-ray diffractometry (PXRD). From the DSC and TG data, it was confirmed that Form 2 is \( {\raise0.5ex\hbox{$\scriptstyle 1$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}} \) methanol solvate, Form 3 is 1 methanol solvate, Form 4 is \( 1{\raise0.5ex\hbox{$\scriptstyle 1$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}} \) ethanol solvate, and Form 5 is \( 3{\raise0.5ex\hbox{$\scriptstyle 2$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}} \) hydrate. The PXRD patterns of five crystal forms were different, respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer at 37 ± 0.5 °C, the solubility of Form 2 was the highest. And the dissolution rate at 5 min in water decreased in rank order: Form 2 > Form 4 > Form 1 > Form 3 > Form 5. After storage of 3 months at 2 °C, 24 % relative humidity, Form 1, Form 2, Form 3, and Form 4 were not transformed, but Form 5 (\( 3{\raise0.5ex\hbox{$\scriptstyle 2$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}} \) hydrate) was transformed to dihydrate.

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Acknowledgements

This study was supported by the research grant from Duksung Women’s University (2014).

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Authors and Affiliations

  1. LG Household & Health Care, 175 Gajeong-Ro, Yuseong-Gu, Daejeon, 305-343, Korea

    Su-Ryun Tak

  2. College of Pharmacy, Duksung Women’s University, 419, Ssangmun-Dong, Dobong-Gu, Seoul, 132-714, Korea

    Young-Taek Sohn

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Correspondence to Young-Taek Sohn.

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Tak, SR., Sohn, YT. Crystal forms of a new 5-HT4 receptor agonist DA-6886. J Therm Anal Calorim 123, 2477–2483 (2016). https://doi.org/10.1007/s10973-015-4897-1

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