<i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies
Dodeca-2<i>E</i>,4<i>E</i>,8<i>Z</i>,10<i>E</i>/<i>Z</i>-tetraenoic isobutylamide (tetraene) is the main component of <i>Echinacea angustifolia</i> DC. lipophilic extract, the bioavailability and immunomodulatory effect after or...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/11/1096 |
| _version_ | 1797547808764461056 |
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| author | Dritan Hasa Simon Žakelj Iztok Grabnar Francesco Cilurzo Stefano Dall’Acqua Antonella Riva Beatrice Perissutti Dario Voinovich |
| author_facet | Dritan Hasa Simon Žakelj Iztok Grabnar Francesco Cilurzo Stefano Dall’Acqua Antonella Riva Beatrice Perissutti Dario Voinovich |
| author_sort | Dritan Hasa |
| collection | DOAJ |
| description | Dodeca-2<i>E</i>,4<i>E</i>,8<i>Z</i>,10<i>E</i>/<i>Z</i>-tetraenoic isobutylamide (tetraene) is the main component of <i>Echinacea angustifolia</i> DC. lipophilic extract, the bioavailability and immunomodulatory effect after oral administration in soft gel capsules in healthy volunteers of which we have already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide. The first step, therefore, encompassed the preparation of a drug-in-adhesive patch with an area of 868 mm<sup>2</sup> and containing a dose of 0.64 mg of tetraene. In vitro skin permeation studies in Franz-type diffusion chambers resulted in a tetraene flux of (103 ± 10) ng × cm<sup>−2</sup> × h<sup>−1</sup> with a very good linearity (r = 0.99). The relatively low lag time of just 13 min indicates low binding and the accumulation of tetraene in the skin. Finally, the patch was administered to six healthy volunteers, and the pharmacokinetic analysis was performed by nonlinear mixed effects modelling with soft gel oral capsules serving as the reference formulation. The in vivo results correlated well with the in vitro permeation and indicated an initial burst tetraene absorption from the patch that was in parallel with the zero-order kinetics of absorption. The rate of the latter process was in good agreement with the one estimated in vitro. The tetraene absorption rate was therefore slow and prolonged with time, resulting in a bioavailability of 39% relative to the soft gel capsules and a very flat plasma concentration profile. |
| first_indexed | 2024-03-10T14:49:32Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:49:32Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-24f8073b23ac492d9bb7ce92d44c66452023-11-20T21:04:11ZengMDPI AGPharmaceutics1999-49232020-11-011211109610.3390/pharmaceutics12111096<i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo StudiesDritan Hasa0Simon Žakelj1Iztok Grabnar2Francesco Cilurzo3Stefano Dall’Acqua4Antonella Riva5Beatrice Perissutti6Dario Voinovich7Department of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127 Trieste, ItalyFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, SloveniaDepartment of Pharmaceutical Sciences, University of Milano, Via G. Colombo, 71-20133 Milano, ItalyDepartment of Pharmaceutical Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, ItalyR&D Indena SpA, Viale Ortles, 12, 20139 Milano, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, P. le Europa 1, 34127 Trieste, ItalyDodeca-2<i>E</i>,4<i>E</i>,8<i>Z</i>,10<i>E</i>/<i>Z</i>-tetraenoic isobutylamide (tetraene) is the main component of <i>Echinacea angustifolia</i> DC. lipophilic extract, the bioavailability and immunomodulatory effect after oral administration in soft gel capsules in healthy volunteers of which we have already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide. The first step, therefore, encompassed the preparation of a drug-in-adhesive patch with an area of 868 mm<sup>2</sup> and containing a dose of 0.64 mg of tetraene. In vitro skin permeation studies in Franz-type diffusion chambers resulted in a tetraene flux of (103 ± 10) ng × cm<sup>−2</sup> × h<sup>−1</sup> with a very good linearity (r = 0.99). The relatively low lag time of just 13 min indicates low binding and the accumulation of tetraene in the skin. Finally, the patch was administered to six healthy volunteers, and the pharmacokinetic analysis was performed by nonlinear mixed effects modelling with soft gel oral capsules serving as the reference formulation. The in vivo results correlated well with the in vitro permeation and indicated an initial burst tetraene absorption from the patch that was in parallel with the zero-order kinetics of absorption. The rate of the latter process was in good agreement with the one estimated in vitro. The tetraene absorption rate was therefore slow and prolonged with time, resulting in a bioavailability of 39% relative to the soft gel capsules and a very flat plasma concentration profile.https://www.mdpi.com/1999-4923/12/11/1096<i>Echinacea angustifolia</i> lipophilic extracttetraenedrug-in-adhesive patchin vitro skin permeationpharmacokinetics |
| spellingShingle | Dritan Hasa Simon Žakelj Iztok Grabnar Francesco Cilurzo Stefano Dall’Acqua Antonella Riva Beatrice Perissutti Dario Voinovich <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies Pharmaceutics <i>Echinacea angustifolia</i> lipophilic extract tetraene drug-in-adhesive patch in vitro skin permeation pharmacokinetics |
| title | <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies |
| title_full | <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies |
| title_fullStr | <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies |
| title_full_unstemmed | <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies |
| title_short | <i>Echinacea angustifolia</i> DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies |
| title_sort | i echinacea angustifolia i dc lipophilic extract patch for skin application preparation in vitro and in vivo studies |
| topic | <i>Echinacea angustifolia</i> lipophilic extract tetraene drug-in-adhesive patch in vitro skin permeation pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/12/11/1096 |
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