Echinacea angustifolia DC. lipophilic extract patch for skin application : preparation, in vitro and in vivo studies

Hasa, Dritan (author), Žakelj, Simon (author), Grabnar, Iztok (author), Cilurzo, Francesco (author), Dall'Acqua, Stefano (author), Riva, Antonella (author), Perissutti, Beatrice (author), Voinovich, Dario (author)

Dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) is the main component of Echinacea angustifolia 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$^2$ 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$^{−2}$ × h$^{−1}$ 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.

• Language: English
• Keywords: Echinacea angustifolia lipophilic extract, tetraene, drug-in-adhesive patch, in vitro skin permeation, pharmacokinetics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 11 str.
• Numbering: Vol. 12, iss. 11, art. 1096
• PID: 20.500.12556/RUL-134661
• UDC: 615.015
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics12111096
• COBISS.SI-ID: 37568515
• Publication date in RUL: 24.01.2022

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 16.11.2020

Secondary language

• Language: Slovenian
• Keywords: lipofilni ekstrakt Echinacea angustifolia, tetraen, zdravilna učinkovina v adhezivnem obližu, prehod skozi kožo in vitro

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: UNITS, Fondo Ricercatori di Ateneo

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih