Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics
Introduction: Modafinil, a wakefulness-promoting agent, is primarily used to treat excessive daytime sleepiness associated with narcolepsy and fatigue. As a BCS class II drug, modafinil exhibits low solubility and high permeability, with its crystalline structure significantly impacting dissolution...
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International Association of Physical Chemists (IAPC)
2025-01-01
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| Series: | ADMET and DMPK |
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| Online Access: | https://pub.iapchem.org/ojs/index.php/admet/article/view/2569 |
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| author | Derar Omari Assayed Sallam Iyad Rashid Shereen M. Assaf Faisal Akayleh Khaldoun A. Al-Sou′od |
| author_facet | Derar Omari Assayed Sallam Iyad Rashid Shereen M. Assaf Faisal Akayleh Khaldoun A. Al-Sou′od |
| author_sort | Derar Omari |
| collection | DOAJ |
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Introduction: Modafinil, a wakefulness-promoting agent, is primarily used to treat excessive daytime sleepiness associated with narcolepsy and fatigue. As a BCS class II drug, modafinil exhibits low solubility and high permeability, with its crystalline structure significantly impacting dissolution, bioavailability, and compressibility. This study explores the use of microwave energy to alter the crystalline structure of modafinil in the presence of Gelucire® 48/16, aiming to improve its pharmaceutical properties. Methods: Modafinil was treated with microwave energy to form complexes with Gelucire® 48/16, and the resulting formulations were compared to hot-melt complexes and physical mixtures. The structural and thermal properties of the complexes were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Compressibility and compactibility were evaluated through Kawakita model analysis and response surface methodolog). The effect of microwaves on molecular interactions was further investigated using molecular modeling. Results: XRPD analysis revealed distinct crystalline patterns for microwave and hot-melt complexes compared to physical mixtures, with increased amorphousness observed through crystallinity, relative crystallinity, and relative intensity parameters. DSC thermograms indicated a reduction in melting endotherms and heat flow, suggesting structural changes due to complex formation. Compressibility and compactibility studies demonstrated optimal performance at low Gelucire® content, with microwave-treated complexes exhibiting superior properties to untreated mixtures. Molecular modeling confirmed dipole-dipole interactions between modafinil and the hydrophilic portion of Gelucire®. Conclusions: The study demonstrates that microwave energy effectively alters the crystalline structure of modafinil in the presence of Gelucire® 48/16, enhancing its amorphousness, compressibility, and compactibility. These findings highlight the potential of microwave-assisted complexation as a novel approach to improve the pharmaceutical performance of BCS Class II drugs like modafinil.
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| format | Article |
| id | doaj-art-237b5e5f72f94f6c83d0334b6de0e4ca |
| institution | Kabale University |
| issn | 1848-7718 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | International Association of Physical Chemists (IAPC) |
| record_format | Article |
| series | ADMET and DMPK |
| spelling | doaj-art-237b5e5f72f94f6c83d0334b6de0e4ca2025-01-21T07:44:52ZengInternational Association of Physical Chemists (IAPC)ADMET and DMPK1848-77182025-01-0110.5599/admet.2569Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristicsDerar Omari0Assayed Sallam1Iyad Rashid2Shereen M. Assaf3Faisal Akayleh4Khaldoun A. Al-Sou′od5Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan. yTQPharma, Amman, JordanTQPharma, Amman, JordanDepartment of Pharmaceutical Technology, Faulty of Pharmacy, Jordan University of Science and Technology, P. O. Box 3030 Irbid 22110, Jordan.Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, JordanDepartment of Chemistry, Faculty of Science, Al Al-Bayt University, P. O. Box 130040, Mafraq, 25113, JORDAN Introduction: Modafinil, a wakefulness-promoting agent, is primarily used to treat excessive daytime sleepiness associated with narcolepsy and fatigue. As a BCS class II drug, modafinil exhibits low solubility and high permeability, with its crystalline structure significantly impacting dissolution, bioavailability, and compressibility. This study explores the use of microwave energy to alter the crystalline structure of modafinil in the presence of Gelucire® 48/16, aiming to improve its pharmaceutical properties. Methods: Modafinil was treated with microwave energy to form complexes with Gelucire® 48/16, and the resulting formulations were compared to hot-melt complexes and physical mixtures. The structural and thermal properties of the complexes were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Compressibility and compactibility were evaluated through Kawakita model analysis and response surface methodolog). The effect of microwaves on molecular interactions was further investigated using molecular modeling. Results: XRPD analysis revealed distinct crystalline patterns for microwave and hot-melt complexes compared to physical mixtures, with increased amorphousness observed through crystallinity, relative crystallinity, and relative intensity parameters. DSC thermograms indicated a reduction in melting endotherms and heat flow, suggesting structural changes due to complex formation. Compressibility and compactibility studies demonstrated optimal performance at low Gelucire® content, with microwave-treated complexes exhibiting superior properties to untreated mixtures. Molecular modeling confirmed dipole-dipole interactions between modafinil and the hydrophilic portion of Gelucire®. Conclusions: The study demonstrates that microwave energy effectively alters the crystalline structure of modafinil in the presence of Gelucire® 48/16, enhancing its amorphousness, compressibility, and compactibility. These findings highlight the potential of microwave-assisted complexation as a novel approach to improve the pharmaceutical performance of BCS Class II drugs like modafinil. https://pub.iapchem.org/ojs/index.php/admet/article/view/2569Tablet compressibilitycrystallinitymolecular modelingcarbonyl oxygen of modafinil |
| spellingShingle | Derar Omari Assayed Sallam Iyad Rashid Shereen M. Assaf Faisal Akayleh Khaldoun A. Al-Sou′od Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics ADMET and DMPK Tablet compressibility crystallinity molecular modeling carbonyl oxygen of modafinil |
| title | Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics |
| title_full | Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics |
| title_fullStr | Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics |
| title_full_unstemmed | Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics |
| title_short | Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics |
| title_sort | microwave coprocessing of modafinil with gelucire r thermal and compression characteristics |
| topic | Tablet compressibility crystallinity molecular modeling carbonyl oxygen of modafinil |
| url | https://pub.iapchem.org/ojs/index.php/admet/article/view/2569 |
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