Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films
To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/5/739 |
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| author | Abdullah A. Alamoudi Osama A. A. Ahmed Khalid M. El-Say |
| author_facet | Abdullah A. Alamoudi Osama A. A. Ahmed Khalid M. El-Say |
| author_sort | Abdullah A. Alamoudi |
| collection | DOAJ |
| description | To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X<sub>1</sub>), the concentration of mixed micelles (MMs) in the film (X<sub>2</sub>), and the concentration of the permeation enhancer (X<sub>3</sub>). The initial permeation of AVA after 1 h (Y<sub>1</sub>), and the cumulative permeation of AVA after 24 h (Y<sub>2</sub>) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug’s permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase (<i>p</i> < 0.05) in the C<sub>max</sub> of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA. |
| first_indexed | 2024-03-10T11:20:05Z |
| format | Article |
| id | doaj.art-82167653b3df462bb0f37e844dfc1402 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:20:05Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-82167653b3df462bb0f37e844dfc14022023-11-21T20:08:23ZengMDPI AGPharmaceutics1999-49232021-05-0113573910.3390/pharmaceutics13050739Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded FilmsAbdullah A. Alamoudi0Osama A. A. Ahmed1Khalid M. El-Say2Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaTo avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X<sub>1</sub>), the concentration of mixed micelles (MMs) in the film (X<sub>2</sub>), and the concentration of the permeation enhancer (X<sub>3</sub>). The initial permeation of AVA after 1 h (Y<sub>1</sub>), and the cumulative permeation of AVA after 24 h (Y<sub>2</sub>) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug’s permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase (<i>p</i> < 0.05) in the C<sub>max</sub> of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA.https://www.mdpi.com/1999-4923/13/5/739bioavailabilityerectile dysfunctiontransdermal filmPDE5 inhibitorsskin permeation |
| spellingShingle | Abdullah A. Alamoudi Osama A. A. Ahmed Khalid M. El-Say Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films Pharmaceutics bioavailability erectile dysfunction transdermal film PDE5 inhibitors skin permeation |
| title | Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films |
| title_full | Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films |
| title_fullStr | Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films |
| title_full_unstemmed | Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films |
| title_short | Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films |
| title_sort | investigating the potential of transdermal delivery of avanafil using vitamin e tpgs based mixed micelles loaded films |
| topic | bioavailability erectile dysfunction transdermal film PDE5 inhibitors skin permeation |
| url | https://www.mdpi.com/1999-4923/13/5/739 |
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