Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature
Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures...
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/84 |
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| author | Shohei Aikawa Hironori Tanaka Hiroshi Ueda Masato Maruyama Kazutaka Higaki |
| author_facet | Shohei Aikawa Hironori Tanaka Hiroshi Ueda Masato Maruyama Kazutaka Higaki |
| author_sort | Shohei Aikawa |
| collection | DOAJ |
| description | Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (<i>Tg</i>) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher <i>Tg</i>. A novel neuropeptide Y<sub>5</sub> receptor antagonist (AntiY<sub>5</sub>R) and NaTC with <i>Tg</i> of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY<sub>5</sub>R and NaTC (AntiY<sub>5</sub>R-NaTC) at various molar ratios. Deviation from the theoretical <i>Tg</i> value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY<sub>5</sub>R and NaTC. AntiY<sub>5</sub>R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY<sub>5</sub>R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules. |
| first_indexed | 2024-03-09T11:28:36Z |
| format | Article |
| id | doaj.art-8c3f3f68c0a24f5e8da8dc2e8b1a2920 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:28:36Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8c3f3f68c0a24f5e8da8dc2e8b1a29202023-11-30T23:57:26ZengMDPI AGPharmaceutics1999-49232022-12-011518410.3390/pharmaceutics15010084Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition TemperatureShohei Aikawa0Hironori Tanaka1Hiroshi Ueda2Masato Maruyama3Kazutaka Higaki4Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, JapanFormulation Research Department, Formulation R&D Laboratory, Shionogi & Co., Ltd., Hyogo 660-0813, JapanBioanalytical, Analysis and Evaluation Laboratory, Shionogi & Co., Ltd., Osaka 561-0825, JapanDepartment of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, JapanDepartment of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, JapanBrick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (<i>Tg</i>) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher <i>Tg</i>. A novel neuropeptide Y<sub>5</sub> receptor antagonist (AntiY<sub>5</sub>R) and NaTC with <i>Tg</i> of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY<sub>5</sub>R and NaTC (AntiY<sub>5</sub>R-NaTC) at various molar ratios. Deviation from the theoretical <i>Tg</i> value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY<sub>5</sub>R and NaTC. AntiY<sub>5</sub>R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY<sub>5</sub>R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.https://www.mdpi.com/1999-4923/15/1/84amorphousco-amorphouscrystallizationsodium taurocholateglass transition temperatureintermolecular interaction |
| spellingShingle | Shohei Aikawa Hironori Tanaka Hiroshi Ueda Masato Maruyama Kazutaka Higaki Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature Pharmaceutics amorphous co-amorphous crystallization sodium taurocholate glass transition temperature intermolecular interaction |
| title | Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature |
| title_full | Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature |
| title_fullStr | Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature |
| title_full_unstemmed | Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature |
| title_short | Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature |
| title_sort | formation of a stable co amorphous system for a brick dust molecule by utilizing sodium taurocholate with high glass transition temperature |
| topic | amorphous co-amorphous crystallization sodium taurocholate glass transition temperature intermolecular interaction |
| url | https://www.mdpi.com/1999-4923/15/1/84 |
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