Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization
Sulpiride (SUL) is a dopamine D<sub>2</sub>-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objec...
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/12/446 |
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| author | Hesham M. Tawfeek Yasser A. Hassan Mohammed F. Aldawsari Mohamed H. Fayed |
| author_facet | Hesham M. Tawfeek Yasser A. Hassan Mohammed F. Aldawsari Mohamed H. Fayed |
| author_sort | Hesham M. Tawfeek |
| collection | DOAJ |
| description | Sulpiride (SUL) is a dopamine D<sub>2</sub>-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A 3<sup>2</sup> full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X<sub>1</sub>) and Prosolv<sup>®</sup> (X<sub>2</sub>) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58 ± 0.52 KP, friability of 0.73 ± 0.158%, disintegration time of 37.5 ± 1.87 s and drug release of 100.51 ± 1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant (<i>p</i> < 0.01) increase in C<sub>max</sub> and AUC(<sub>0–∞</sub>) and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action. |
| first_indexed | 2024-03-10T14:18:22Z |
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| id | doaj.art-5792717cc4424cb0acb7823136ed6165 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T14:18:22Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-5792717cc4424cb0acb7823136ed61652023-11-20T23:36:40ZengMDPI AGPharmaceuticals1424-82472020-12-01131244610.3390/ph13120446Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo CharacterizationHesham M. Tawfeek0Yasser A. Hassan1Mohammed F. Aldawsari2Mohamed H. Fayed3Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35523, EgyptDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaSulpiride (SUL) is a dopamine D<sub>2</sub>-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A 3<sup>2</sup> full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X<sub>1</sub>) and Prosolv<sup>®</sup> (X<sub>2</sub>) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58 ± 0.52 KP, friability of 0.73 ± 0.158%, disintegration time of 37.5 ± 1.87 s and drug release of 100.51 ± 1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant (<i>p</i> < 0.01) increase in C<sub>max</sub> and AUC(<sub>0–∞</sub>) and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action.https://www.mdpi.com/1424-8247/13/12/446sulpiridefast disintegrating tabletsdopamine antagonistfactorial designProsolve<sup>®</sup>bioavailability |
| spellingShingle | Hesham M. Tawfeek Yasser A. Hassan Mohammed F. Aldawsari Mohamed H. Fayed Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization Pharmaceuticals sulpiride fast disintegrating tablets dopamine antagonist factorial design Prosolve<sup>®</sup> bioavailability |
| title | Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization |
| title_full | Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization |
| title_fullStr | Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization |
| title_full_unstemmed | Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization |
| title_short | Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization |
| title_sort | enhancing the low oral bioavailability of sulpiride via fast orally disintegrating tablets formulation optimization and in vivo characterization |
| topic | sulpiride fast disintegrating tablets dopamine antagonist factorial design Prosolve<sup>®</sup> bioavailability |
| url | https://www.mdpi.com/1424-8247/13/12/446 |
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