Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen
Since its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: t...
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/713 |
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| author | Heba A. Abou-Taleb Mai E. Shoman Tarek Saad Makram Jelan A. Abdel-Aleem Hamdy Abdelkader |
| author_facet | Heba A. Abou-Taleb Mai E. Shoman Tarek Saad Makram Jelan A. Abdel-Aleem Hamdy Abdelkader |
| author_sort | Heba A. Abou-Taleb |
| collection | DOAJ |
| description | Since its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: tris, L-lysine, and L-arginine, and investigated their ability to improve water solubility and reduce ulcerogenic potential. The complexation/salt formation of ketoprofen and the basic excipients was prepared using physical mixing and coprecipitation methods. The prepared mixtures were studied for solubility, docking, dissolution, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vivo evaluation for efficacy (the writhing test), and safety (ulcerogenic liability). Phase solubility diagrams were constructed, and a linear solubility (AL type) curve was obtained with tris. Docking studies suggested a possible salt formation with L-arginine using Hirshfeld surface analysis. The order of enhancement of solubility and dissolution rates was as follows: L-arginine > L-lysine > tris. In vivo analgesic evaluation indicated a significant enhancement of the onset of action of analgesic activities for the three basic excipients. However, safety and gastric protection indicated that both ketoprofen arginine and ketoprofen lysine salts were more favorable than ketoprofen tris. |
| first_indexed | 2024-03-11T08:15:33Z |
| format | Article |
| id | doaj.art-1f1f12e6d32c4d19a4bcfa2386969ac3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:15:33Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-1f1f12e6d32c4d19a4bcfa2386969ac32023-11-16T22:43:37ZengMDPI AGPharmaceutics1999-49232023-02-0115271310.3390/pharmaceutics15020713Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug KetoprofenHeba A. Abou-Taleb0Mai E. Shoman1Tarek Saad Makram2Jelan A. Abdel-Aleem3Hamdy Abdelkader4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University (MUE), Sohag 82755, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, October 6 12585, EgyptDepartment of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61441, Saudi ArabiaSince its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: tris, L-lysine, and L-arginine, and investigated their ability to improve water solubility and reduce ulcerogenic potential. The complexation/salt formation of ketoprofen and the basic excipients was prepared using physical mixing and coprecipitation methods. The prepared mixtures were studied for solubility, docking, dissolution, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vivo evaluation for efficacy (the writhing test), and safety (ulcerogenic liability). Phase solubility diagrams were constructed, and a linear solubility (AL type) curve was obtained with tris. Docking studies suggested a possible salt formation with L-arginine using Hirshfeld surface analysis. The order of enhancement of solubility and dissolution rates was as follows: L-arginine > L-lysine > tris. In vivo analgesic evaluation indicated a significant enhancement of the onset of action of analgesic activities for the three basic excipients. However, safety and gastric protection indicated that both ketoprofen arginine and ketoprofen lysine salts were more favorable than ketoprofen tris.https://www.mdpi.com/1999-4923/15/2/713ketoprofenL-arginineL-lysinetrisbasic amino acidswrithing |
| spellingShingle | Heba A. Abou-Taleb Mai E. Shoman Tarek Saad Makram Jelan A. Abdel-Aleem Hamdy Abdelkader Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen Pharmaceutics ketoprofen L-arginine L-lysine tris basic amino acids writhing |
| title | Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen |
| title_full | Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen |
| title_fullStr | Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen |
| title_full_unstemmed | Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen |
| title_short | Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen |
| title_sort | exploration of the safety and solubilization dissolution analgesic effects of common basic excipients on the nsaid drug ketoprofen |
| topic | ketoprofen L-arginine L-lysine tris basic amino acids writhing |
| url | https://www.mdpi.com/1999-4923/15/2/713 |
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