Back to Search Start Over

Self-Emulsifying Formulations to Increase the Oral Bioavailability of 4,6,4′-Trimethylangelicin as a Possible Treatment for Cystic Fibrosis

Authors :
Erica Franceschinis
Marco Roverso
Daniela Gabbia
Sara De Martin
Matteo Brusegan
Christian Vaccarin
Sara Bogialli
Adriana Chilin
Source :
Pharmaceutics, Vol 14, Iss 9, p 1806 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

4,6,4′-trimethylangelicin (TMA) is a promising pharmacological option for the treatment of cystic fibrosis (CF) due to its triple-acting behavior toward the function of the CF transmembrane conductance regulator. It is a poorly water-soluble drug, and thus it is a candidate for developing a self-emulsifying formulation (SEDDS). This study aimed to develop a SEDDS to improve the oral bioavailability of TMA. Excipients were selected on the basis of solubility studies. Polyoxyl-35 castor oil (Cremophor® EL) was proposed as surfactant, diethylene glycol-monoethyl ether (Transcutol® HP) as cosolvent, and a mixture of long-chainmono-,di-, and triglycerides (Maisine® CC) or medium-chain triglycerides (LabrafacTM lipophile) as oil phases. Different mixtures were prepared and characterized by measuring the emulsification time, drop size, and polydispersity index to identify the most promising formulation. Two formulations containing 50% surfactant (w/w), 40% cosolvent (w/w), and 10% oil (w/w) (Maisine® CC or LabrafacTM lipophile) were selected. The results showed that both formulations were able to self-emulsify, producing nanoemulsions with a drop size range of 20–25 nm, and in vivo pharmacokinetic studies demonstrated that they were able to significantly increase the oral bioavailability of TMA. In conclusion, SEEDS are useful tools to ameliorate the pharmacokinetic profile of TMA and could represent a strategy to improve the therapeutic management of CF.

Details

Language :
English
ISSN :
19994923
Volume :
14
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.6324eab598142c9ad87a0b77ebfc284
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics14091806