Daiki Umeda

Solubility improvement of epalrestat by layered structure formation via cocrystallization

Epalrestat, a drug for diabetic neuropathy, was able to form a cocrystal with a pharmaceutically acceptable coformer of caffeine. The cocrystal was characterized using powder X-ray diffraction and infrared spectroscopy, and the structure was determined using single crystal structure analysis. Pharmaceutically relevant physicochemical properties such as solubility, dissolution rate, and physical stability were evaluated. The cocrystal exhibited higher solubility and faster dissolution than the parent drug material. This improvement corresponded to the formation of a layered structure in the cocrystal, wherein a chain consisting of epalrestat molecules is sandwiched between caffeine molecules. The cocrystal also exhibited physical stability during a slurry experiment in most organic solvents, except in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) solvents. In these solvents, the cocrystals underwent disproportionation into caffeine and epalrestat solvates (DMF and DMSO), and the crystal structures of epalerstat DMF and DMSO solvates are also reported in this study.

Improving mechanical properties of desloratadine via multicomponent crystal formation

ABSTRACT We report the first multicomponent crystal of desloratadine, an important anti‐histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine‐benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine‐benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference. Graphical abstract Figure. No Caption available.

Solubility Improvement of Benexate through Salt Formation Using Artificial Sweetener

Benexate, a drug used clinically as a defensive type anti-ulcer agent, has poor solubility and a bitter taste. To improve its solubility, a crystal engineering approach was proposed with the formation of novel salts using an artificial sweetener as a salt co-former. This was also expected to address the bitter taste of the drug. In this work, we report on the preparation and evaluation of the physicochemical properties of the novel salts benexate saccharinate monohydrate and benexate cyclamate whose crystal structures were determined by single-crystal X-ray structure analysis. These novel salts showed higher solubility and faster dissolution profiles that were associated with the occurrence of local layered-like structures. They also showed better moisture uptake profiles and were classified as non-hygroscopic materials. Therefore, benexate saccharinate monohydrate and benexate cyclamate expedited the development of sweet pharmaceutical salts of benexate with improved performances.

CCDC 1531870: Experimental Crystal Structure Determination

Related Article: Okky Dwichandra Putra, Daiki Umeda, Yuda Prasetya Nugraha, Takayuki Furuishi, Hiromasa Nagase, Kaori Fukuzawa, Hidehiro Uekusa, Etsuo Yonemochi||CrystEngComm|||doi:10.1039/C7CE00284J

A new solvate of epalerstat, a drug for diabetic neuropathy

The title compound, epalerstat acetone monosolvate, is isotypic with the previously reported tetrahydrofuran solvate.

Epalrestat tetra­hydro­furan monosolvate: crystal structure and phase transition

Epalrestat, an important drug for diabetic neuropathy, has been reported to exist in polymphic, solvated and co-crystal forms. Herein, we report on the crystal structure of epalerstat tetrahydrofuran solvate which crystallizes in the triclinic space group P . On desolvation, epalerstat Form II (monoclinic, C2/c) is obtained.