Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts
Investigation on the solid-state pharmaceutical chemistry has been known as an intriguing strategy to not only modify the physicochemical properties of drugs but also expand the solid form landscape. Vortioxetine (VOT) is an effective but poorly soluble antidepressant. To improve the solubility of v...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/9/10/536 |
| _version_ | 1811262343517044736 |
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| author | Xian-Rui Zhang Lei Gao Gui-Yuan He Chao-Jie Chen |
| author_facet | Xian-Rui Zhang Lei Gao Gui-Yuan He Chao-Jie Chen |
| author_sort | Xian-Rui Zhang |
| collection | DOAJ |
| description | Investigation on the solid-state pharmaceutical chemistry has been known as an intriguing strategy to not only modify the physicochemical properties of drugs but also expand the solid form landscape. Vortioxetine (VOT) is an effective but poorly soluble antidepressant. To improve the solubility of vortioxetine and expand possible solid forms, in this paper, four novel solid forms of vortioxetine with dihydroxybenzoic acids (VOT-23BA, VOT-24BA-TOL, VOT-25BA, and VOT-26BA, 23BA = 2,3-dihydroxybenzoic acid, 24BA = 2,4-dihydroxybenzoic acid, 25BA = 2,5-dihydroxybenzoic acid, 26BA = 2,6-dihydroxybenzoic acid, and TOL = toluene) were synthesized first by a solvent evaporation method and then characterized by single-crystal X-ray diffraction (SCXRD), thermal, and XRD techniques. VOT-24BA-TOL, VOT-25BA, and VOT-26BA, showed similar [2+2] tetrameric <inline-formula> <math display="inline"> <semantics> <msubsup> <mi mathvariant="normal">R</mi> <mn>4</mn> <mn>4</mn> </msubsup> </semantics> </math> </inline-formula> (12) hydrogen bonds by acid-piperazine heterosynthon. In the VOT-23BA-H<sub>2</sub>O salt, the VOT cation and 23BA anion interacted through protonated piperazine-hydroxyl N-H···O hydrogen bonds, not protonated piperazine-deprotonated carboxylic acid N-H···O hydrogen bonds. Solubility studies were carried out in purified water and it was found that the VOT-23BA-H<sub>2</sub>O, VOT-25BA, and VOT-26BA salts exhibited an increase in water compared to pure VOT. The solubility of the stabilized salt formations followed the order of VOT-25BA > VOT-26BA > VOT-23BA-H<sub>2</sub>O in purified water. |
| first_indexed | 2024-04-12T19:23:38Z |
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| id | doaj.art-205fe2f22017417b8f05b5307a08d688 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-04-12T19:23:38Z |
| publishDate | 2019-10-01 |
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| series | Crystals |
| spelling | doaj.art-205fe2f22017417b8f05b5307a08d6882022-12-22T03:19:32ZengMDPI AGCrystals2073-43522019-10-0191053610.3390/cryst9100536cryst9100536Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal ContactsXian-Rui Zhang0Lei Gao1Gui-Yuan He2Chao-Jie Chen3School of Chemical Engineering and resource recycling, Wuzhou University, Wuzhou 543000, ChinaSchool of Chemical Engineering and resource recycling, Wuzhou University, Wuzhou 543000, ChinaSchool of Chemical Engineering and resource recycling, Wuzhou University, Wuzhou 543000, ChinaSchool of Chemical Engineering and resource recycling, Wuzhou University, Wuzhou 543000, ChinaInvestigation on the solid-state pharmaceutical chemistry has been known as an intriguing strategy to not only modify the physicochemical properties of drugs but also expand the solid form landscape. Vortioxetine (VOT) is an effective but poorly soluble antidepressant. To improve the solubility of vortioxetine and expand possible solid forms, in this paper, four novel solid forms of vortioxetine with dihydroxybenzoic acids (VOT-23BA, VOT-24BA-TOL, VOT-25BA, and VOT-26BA, 23BA = 2,3-dihydroxybenzoic acid, 24BA = 2,4-dihydroxybenzoic acid, 25BA = 2,5-dihydroxybenzoic acid, 26BA = 2,6-dihydroxybenzoic acid, and TOL = toluene) were synthesized first by a solvent evaporation method and then characterized by single-crystal X-ray diffraction (SCXRD), thermal, and XRD techniques. VOT-24BA-TOL, VOT-25BA, and VOT-26BA, showed similar [2+2] tetrameric <inline-formula> <math display="inline"> <semantics> <msubsup> <mi mathvariant="normal">R</mi> <mn>4</mn> <mn>4</mn> </msubsup> </semantics> </math> </inline-formula> (12) hydrogen bonds by acid-piperazine heterosynthon. In the VOT-23BA-H<sub>2</sub>O salt, the VOT cation and 23BA anion interacted through protonated piperazine-hydroxyl N-H···O hydrogen bonds, not protonated piperazine-deprotonated carboxylic acid N-H···O hydrogen bonds. Solubility studies were carried out in purified water and it was found that the VOT-23BA-H<sub>2</sub>O, VOT-25BA, and VOT-26BA salts exhibited an increase in water compared to pure VOT. The solubility of the stabilized salt formations followed the order of VOT-25BA > VOT-26BA > VOT-23BA-H<sub>2</sub>O in purified water.https://www.mdpi.com/2073-4352/9/10/536vortioxetinedihydroxybenzoic acidssaltcrystal structuresolubility |
| spellingShingle | Xian-Rui Zhang Lei Gao Gui-Yuan He Chao-Jie Chen Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts Crystals vortioxetine dihydroxybenzoic acids salt crystal structure solubility |
| title | Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts |
| title_full | Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts |
| title_fullStr | Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts |
| title_full_unstemmed | Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts |
| title_short | Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts |
| title_sort | investigations on the solubility of vortioxetine based on x ray structural data and crystal contacts |
| topic | vortioxetine dihydroxybenzoic acids salt crystal structure solubility |
| url | https://www.mdpi.com/2073-4352/9/10/536 |
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