Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies
Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels....
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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/1999-4923/13/5/682 |
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| author | Mahmoud H. Teaima Mohamed Azmi Ahmed Mohamed Randa Tag Abd El Rehem Saadia A. Tayel Mohamed A. El-Nabarawi Shahinaze A. Fouad |
| author_facet | Mahmoud H. Teaima Mohamed Azmi Ahmed Mohamed Randa Tag Abd El Rehem Saadia A. Tayel Mohamed A. El-Nabarawi Shahinaze A. Fouad |
| author_sort | Mahmoud H. Teaima |
| collection | DOAJ |
| description | Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve<sup>®</sup> hydrogel (F7) showed a 1.5-fold increase in Q<sub>180</sub>, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor<sup>®</sup> Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of C<sub>max</sub> and AUC<sub>0–40</sub>, respectively compared to Concor<sup>®</sup> tablets, as well as a smaller T<sub>max</sub> (2.00 ± 2.00 h). The relative bioavailability of F7 was found to be 201.44%, relative to Concor<sup>®</sup> tablets, demonstrating the significantly enhanced transdermal permeation of BH from the selected hydrogel by iontophoresis, in human volunteers. Finally, results showed the successful utility of permeation enhancers combined with iontophoresis in significantly enhanced transdermal permeation of BH, despite its large molecular weight and hydrophilic nature. Therefore, this strategy could be employed as a successful alternative route of administration to conventional oral tablets. |
| first_indexed | 2024-03-10T11:35:02Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:35:02Z |
| publishDate | 2021-05-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-dc20e1d13c9b4c188da8545db0ee72602023-11-21T18:57:00ZengMDPI AGPharmaceutics1999-49232021-05-0113568210.3390/pharmaceutics13050682Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic StudiesMahmoud H. Teaima0Mohamed Azmi Ahmed Mohamed1Randa Tag Abd El Rehem2Saadia A. Tayel3Mohamed A. El-Nabarawi4Shahinaze A. Fouad5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptObour Pharmaceutical Industries, Cairo 13024, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Ahram Canadian University, Giza 19228, EgyptBisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve<sup>®</sup> hydrogel (F7) showed a 1.5-fold increase in Q<sub>180</sub>, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor<sup>®</sup> Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of C<sub>max</sub> and AUC<sub>0–40</sub>, respectively compared to Concor<sup>®</sup> tablets, as well as a smaller T<sub>max</sub> (2.00 ± 2.00 h). The relative bioavailability of F7 was found to be 201.44%, relative to Concor<sup>®</sup> tablets, demonstrating the significantly enhanced transdermal permeation of BH from the selected hydrogel by iontophoresis, in human volunteers. Finally, results showed the successful utility of permeation enhancers combined with iontophoresis in significantly enhanced transdermal permeation of BH, despite its large molecular weight and hydrophilic nature. Therefore, this strategy could be employed as a successful alternative route of administration to conventional oral tablets.https://www.mdpi.com/1999-4923/13/5/682bisoprolol hemifumarate (BH)hypertensionhydrogelsex vivo permeationpermeation enhancersrat skin |
| spellingShingle | Mahmoud H. Teaima Mohamed Azmi Ahmed Mohamed Randa Tag Abd El Rehem Saadia A. Tayel Mohamed A. El-Nabarawi Shahinaze A. Fouad Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies Pharmaceutics bisoprolol hemifumarate (BH) hypertension hydrogels ex vivo permeation permeation enhancers rat skin |
| title | Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies |
| title_full | Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies |
| title_fullStr | Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies |
| title_full_unstemmed | Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies |
| title_short | Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies |
| title_sort | enhanced transdermal delivery of bisoprolol hemifumarate via combined effect of iontophoresis and chemical enhancers ex vivo permeation in vivo pharmacokinetic studies |
| topic | bisoprolol hemifumarate (BH) hypertension hydrogels ex vivo permeation permeation enhancers rat skin |
| url | https://www.mdpi.com/1999-4923/13/5/682 |
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