Imiquimod Solubility in Different Solvents: An Interpretative Approach
Imiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray dryin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/2/282 |
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| author | Daisy Sorgi Andrea Sartori Saveria Germani Rosita Nicolella Gentile Annalisa Bianchera Ruggero Bettini |
| author_facet | Daisy Sorgi Andrea Sartori Saveria Germani Rosita Nicolella Gentile Annalisa Bianchera Ruggero Bettini |
| author_sort | Daisy Sorgi |
| collection | DOAJ |
| description | Imiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray drying; thus, water, ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide were tested at different temperatures. Temperature variations, stirring intensity, and the contact time between IMQ and the solvent greatly affected the evaluation of IMQ equilibrium solubility. The attainment of the solid–liquid equilibrium requires 13 days starting from solid IMQ and 2 days from a cooled-down supersaturated IMQ solution. A correlation between IMQ solubility and the solubility parameters of solvents was not found. IMQ solutions in water, ethanol, methanol, acetonitrile, and dimethyl sulfoxide were neither ideal nor regular. The Scatchard–Hildebrand equation does not apply to IMQ solutions because of association phenomena due to intermolecular hydrogen bonds and/or π-stacking, as supported by the hyperchromic effect that was very pronounced in highly polar solvents, such as water, with the increase in temperature. Finally, IMQ solubility values measured in acetone cannot be considered reliable due to the reaction with the solvent, leading to the formation of new molecules. |
| first_indexed | 2024-03-07T22:18:00Z |
| format | Article |
| id | doaj.art-7c3f63cd166c472f972dda466a743f98 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-07T22:18:00Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7c3f63cd166c472f972dda466a743f982024-02-23T15:31:18ZengMDPI AGPharmaceutics1999-49232024-02-0116228210.3390/pharmaceutics16020282Imiquimod Solubility in Different Solvents: An Interpretative ApproachDaisy Sorgi0Andrea Sartori1Saveria Germani2Rosita Nicolella Gentile3Annalisa Bianchera4Ruggero Bettini5Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyFood and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyImiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray drying; thus, water, ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide were tested at different temperatures. Temperature variations, stirring intensity, and the contact time between IMQ and the solvent greatly affected the evaluation of IMQ equilibrium solubility. The attainment of the solid–liquid equilibrium requires 13 days starting from solid IMQ and 2 days from a cooled-down supersaturated IMQ solution. A correlation between IMQ solubility and the solubility parameters of solvents was not found. IMQ solutions in water, ethanol, methanol, acetonitrile, and dimethyl sulfoxide were neither ideal nor regular. The Scatchard–Hildebrand equation does not apply to IMQ solutions because of association phenomena due to intermolecular hydrogen bonds and/or π-stacking, as supported by the hyperchromic effect that was very pronounced in highly polar solvents, such as water, with the increase in temperature. Finally, IMQ solubility values measured in acetone cannot be considered reliable due to the reaction with the solvent, leading to the formation of new molecules.https://www.mdpi.com/1999-4923/16/2/282imiquimodequilibrium solubilityhyperchromic effectmolecular association |
| spellingShingle | Daisy Sorgi Andrea Sartori Saveria Germani Rosita Nicolella Gentile Annalisa Bianchera Ruggero Bettini Imiquimod Solubility in Different Solvents: An Interpretative Approach Pharmaceutics imiquimod equilibrium solubility hyperchromic effect molecular association |
| title | Imiquimod Solubility in Different Solvents: An Interpretative Approach |
| title_full | Imiquimod Solubility in Different Solvents: An Interpretative Approach |
| title_fullStr | Imiquimod Solubility in Different Solvents: An Interpretative Approach |
| title_full_unstemmed | Imiquimod Solubility in Different Solvents: An Interpretative Approach |
| title_short | Imiquimod Solubility in Different Solvents: An Interpretative Approach |
| title_sort | imiquimod solubility in different solvents an interpretative approach |
| topic | imiquimod equilibrium solubility hyperchromic effect molecular association |
| url | https://www.mdpi.com/1999-4923/16/2/282 |
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