Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization?
In this study, we compare the mechanochemical and classical solvent crystallization methods for forming maleates of GABA and its pharmaceutically active derivatives: Pregabalin, Gabapentin, Phenibut, and Baclofen. Common characterization techniques, like powder and single crystal X-ray diffraction,...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Materials |
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| Online Access: | https://www.mdpi.com/1996-1944/16/6/2242 |
| _version_ | 1797610501641863168 |
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| author | Daniel Komisarek Ebru Taskiran Vera Vasylyeva |
| author_facet | Daniel Komisarek Ebru Taskiran Vera Vasylyeva |
| author_sort | Daniel Komisarek |
| collection | DOAJ |
| description | In this study, we compare the mechanochemical and classical solvent crystallization methods for forming maleates of GABA and its pharmaceutically active derivatives: Pregabalin, Gabapentin, Phenibut, and Baclofen. Common characterization techniques, like powder and single crystal X-ray diffraction, IR-spectroscopy, differential scanning calorimetry, thermogravimetric analysis and <sup>1</sup>H-NMR spectroscopy, are used for the evaluation of structural and physicochemical properties. Our work shows that maleate formation is possible with all investigated target compounds. Large increases in solubility can be achieved, especially for Pregabalin, where up to twentyfold higher solubility in its maleate compared to the pure form can be reached. We furthermore compare the mechanochemical and solvent crystallization regarding quickness, reliability of phase production, and overall product quality. A synthetic route is shown to have an impact on certain properties such as melting point or solubility of the same obtained products, e.g., for Gabapentin and Pregabalin, or lead to the formation of hydrates vs. anhydrous forms. For the GABA and Baclofen maleates, the method of crystallization is not important, and similarly, good results can be obtained by either route. In contrast, Phenibut maleate cannot be obtained pure and single-phase by either method. Our work aims to elucidate promising candidates for the multicomponent crystal formation of blockbuster GABA pharmaceuticals and highlight the usefulness of mechanochemical production routes. |
| first_indexed | 2024-03-11T06:15:11Z |
| format | Article |
| id | doaj.art-43bb3a6100d943c1b6ceb3633eef2b7a |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-11T06:15:11Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-43bb3a6100d943c1b6ceb3633eef2b7a2023-11-17T12:19:29ZengMDPI AGMaterials1996-19442023-03-01166224210.3390/ma16062242Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization?Daniel Komisarek0Ebru Taskiran1Vera Vasylyeva2Inorganic and Structural Chemistry I, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInorganic and Structural Chemistry I, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInorganic and Structural Chemistry I, Heinrich-Heine-University, 40225 Düsseldorf, GermanyIn this study, we compare the mechanochemical and classical solvent crystallization methods for forming maleates of GABA and its pharmaceutically active derivatives: Pregabalin, Gabapentin, Phenibut, and Baclofen. Common characterization techniques, like powder and single crystal X-ray diffraction, IR-spectroscopy, differential scanning calorimetry, thermogravimetric analysis and <sup>1</sup>H-NMR spectroscopy, are used for the evaluation of structural and physicochemical properties. Our work shows that maleate formation is possible with all investigated target compounds. Large increases in solubility can be achieved, especially for Pregabalin, where up to twentyfold higher solubility in its maleate compared to the pure form can be reached. We furthermore compare the mechanochemical and solvent crystallization regarding quickness, reliability of phase production, and overall product quality. A synthetic route is shown to have an impact on certain properties such as melting point or solubility of the same obtained products, e.g., for Gabapentin and Pregabalin, or lead to the formation of hydrates vs. anhydrous forms. For the GABA and Baclofen maleates, the method of crystallization is not important, and similarly, good results can be obtained by either route. In contrast, Phenibut maleate cannot be obtained pure and single-phase by either method. Our work aims to elucidate promising candidates for the multicomponent crystal formation of blockbuster GABA pharmaceuticals and highlight the usefulness of mechanochemical production routes.https://www.mdpi.com/1996-1944/16/6/2242solubilitycrystal engineeringmechanochemistrycrystal synthesis |
| spellingShingle | Daniel Komisarek Ebru Taskiran Vera Vasylyeva Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? Materials solubility crystal engineering mechanochemistry crystal synthesis |
| title | Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? |
| title_full | Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? |
| title_fullStr | Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? |
| title_full_unstemmed | Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? |
| title_short | Maleic Acid as a Co-Former for Pharmaceutically Active GABA Derivatives: Mechanochemistry or Solvent Crystallization? |
| title_sort | maleic acid as a co former for pharmaceutically active gaba derivatives mechanochemistry or solvent crystallization |
| topic | solubility crystal engineering mechanochemistry crystal synthesis |
| url | https://www.mdpi.com/1996-1944/16/6/2242 |
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