# Investigation of the Binary System of Proxyphylline Enantiomers: Phase Diagram Determination

Clément Pinètre, Lina Harfouche, Clément Brandel, Yohann Cartigny, Nicolas

Couvrat, Valerie Dupray

<figure><img src="image_1.png" /></figure>

► To cite this version:

Clément Pinètre, Lina Harfouche, Clément Brandel, Yohann Cartigny, Nicolas Couvrat, et al. Investigation of the Binary System of Proxyphylline Enantiomers: Phase Diagram Determination. Journées d'Etude des Equilibres entre Phases JEEP2023, Oct 2023, Rouen (FR), France. 2023. hal-04233624

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<figure><img src="image_2.png" /></figure>

# Investigation of the Binary System of Proxyphylline Enantiomers: Phase Diagram Determination

C. Pinètre, L. Harfouche, C. Brandel, Y. Cartigny, N. Couvrat, V. Dupray

Univ Rouen Normandie, Normandie Univ, SMS, UR 3233, F-76000 Rouen, France

clement.pinetre1@univ-rouen.fr

## Introduction

Proxyphylline :

* Xanthine-based chiral API derived from Theophylline

* Vasodilator, cardiac stimulant and bronchodilator

Three different “modifications” of the racemic composition highlighted by Griesser *et al.*[1]

* Mod. I (melting at 133.5°C),

* Mod. II (melting at 113.5°C)

* Mod. III (melting at ca. 82-85°C)

Solid-state classifications?

Crystallization-enhanced chiral resolution by Harfouche *et al.*[2]:

* Preferential crystallization on a metastable conglomerate of Proxyphylline

**Identification and Investigations of the different phases involved in this heterogeneous system**

<figure><img src="image_3.png" /></figure>

Molecular structure of Proxyphylline

<figure><img src="image_4.png" /></figure>

Red and orange dashed lines : Predicted

<footnote>[1] U. J. Griesser, M. E. Auer, A. Burger. Micro-Thermal Analysis, FTIR- and Raman-Microscopy of (R,S)-Proxyphylline Crystal Forms, *Microchemical Journal* **2000**, 65, 283-292</footnote>

<footnote>[2] L. C. Harfouche, C. Brandel, Y. Cartigny, J. H. ter Horst, G. Coquerel, S. Petit, *Mol. Pharmaceutics* **2019**, *16*, 4670-4676.</footnote>

<footnote>[3] Jacques, J.; Collet, A.; Wilen, S. H. *Enantiomers, Racemates, and Resolutions*; Krieger Publishing Company, 1994.</footnote>