Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation
The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol<sup>®</sup> HP–water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelbla...
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MDPI AG
2021-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/2/390 |
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| author | Maharjan Ravi Tripathi Julu Nam Ah Kim Kyeung Eui Park Seong Hoon Jeong |
| author_facet | Maharjan Ravi Tripathi Julu Nam Ah Kim Kyeung Eui Park Seong Hoon Jeong |
| author_sort | Maharjan Ravi |
| collection | DOAJ |
| description | The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol<sup>®</sup> HP–water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van’t Hoff, Buchowski–Ksiazaczak <i>λh</i>, Yalkowsky, and Jouyban–Acree van’t Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosuspension formation using liquid anti-solvent precipitation. Thermodynamic solubility of ABN401 increased significantly with the increase in temperature and maximum solubility was obtained with Transcutol<sup>®</sup> HP while low solubility in was obtained water. An activity coefficient study indicated that high molecular interaction was observed in ABN401–Transcutol<sup>®</sup> HP (THP). The solubility increased proportionately as the mole fraction of Transcutol<sup>®</sup> HP increased in TWM, which was also supported by a solvent effect study. The result suggested endothermic and entropy-driven dissolution. Based on the solubility, nanosuspension was designed with Transcutol<sup>®</sup> HP as solvent, and water as anti-solvent. The mean particle size of nanosuspension decreased to 43.05 nm when the mole fraction of ABN401 in THP, and mole fraction of ABN401 in TWM mixture were decreased to 0.04 and 0.1. The ultrasonicated nanosuspension appeared to give comparatively higher dissolution than micronized nanosuspension and provide a candidate formulation for in vivo purposes. |
| first_indexed | 2024-03-09T04:56:26Z |
| format | Article |
| id | doaj.art-ac33d0cf26c5436d9d912ceb0b2ce391 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:56:26Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ac33d0cf26c5436d9d912ceb0b2ce3912023-12-03T13:05:10ZengMDPI AGMolecules1420-30492021-01-0126239010.3390/molecules26020390Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension FormulationMaharjan Ravi0Tripathi Julu1Nam Ah Kim2Kyeung Eui Park3Seong Hoon Jeong4BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, KoreaBK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, KoreaBK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, KoreaR&D Center, ABION Inc., Seoul 08394, KoreaBK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, KoreaThe solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol<sup>®</sup> HP–water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van’t Hoff, Buchowski–Ksiazaczak <i>λh</i>, Yalkowsky, and Jouyban–Acree van’t Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosuspension formation using liquid anti-solvent precipitation. Thermodynamic solubility of ABN401 increased significantly with the increase in temperature and maximum solubility was obtained with Transcutol<sup>®</sup> HP while low solubility in was obtained water. An activity coefficient study indicated that high molecular interaction was observed in ABN401–Transcutol<sup>®</sup> HP (THP). The solubility increased proportionately as the mole fraction of Transcutol<sup>®</sup> HP increased in TWM, which was also supported by a solvent effect study. The result suggested endothermic and entropy-driven dissolution. Based on the solubility, nanosuspension was designed with Transcutol<sup>®</sup> HP as solvent, and water as anti-solvent. The mean particle size of nanosuspension decreased to 43.05 nm when the mole fraction of ABN401 in THP, and mole fraction of ABN401 in TWM mixture were decreased to 0.04 and 0.1. The ultrasonicated nanosuspension appeared to give comparatively higher dissolution than micronized nanosuspension and provide a candidate formulation for in vivo purposes.https://www.mdpi.com/1420-3049/26/2/390transcutol<sup>®</sup> HPthermodynamicssolubilitynanosuspensionmathematical modelsprecipitation |
| spellingShingle | Maharjan Ravi Tripathi Julu Nam Ah Kim Kyeung Eui Park Seong Hoon Jeong Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation Molecules transcutol<sup>®</sup> HP thermodynamics solubility nanosuspension mathematical models precipitation |
| title | Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation |
| title_full | Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation |
| title_fullStr | Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation |
| title_full_unstemmed | Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation |
| title_short | Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation |
| title_sort | solubility determination of c met inhibitor in solvent mixtures and mathematical modeling to develop nanosuspension formulation |
| topic | transcutol<sup>®</sup> HP thermodynamics solubility nanosuspension mathematical models precipitation |
| url | https://www.mdpi.com/1420-3049/26/2/390 |
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