Development and Characterization of Eudragit®-Based Electrospun Nanofibrous Mats and Their Formulation into Nanofiber Tablets for the Modified Release of Furosemide.

Marilena Vlachou,Efstathia Ioannou,Vassilios Roussis,Stefanos Kikionis,Andrew Tsotinis,Angeliki Siamidi,Sotiria Kyriakou

doi:10.3390/pharmaceutics11090480

Marilena Vlachou, Efstathia Ioannou + Show 5 more

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https://doi.org/10.3390/pharmaceutics11090480

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Journal: Pharmaceutics	Publication Date: Sep 17, 2019
Citations: 27	License type: CC BY 4.0

Affiliation: National and Kapodistrian University of Athens

Abstract

Furosemide, a chloride channel blocker ordinarily used as a high-ceiling or loop diuretic, is practically insoluble in water and dilute acids. Due to its acidic nature, furosemide is mostly absorbed in the stomach and in the upper small intestine. Efforts have focused on the development of sustained release systems of furosemide in order to improve the effectiveness of the drug, which exhibits poor aqueous solubility and poor permeability. Recently, electrospun nanofibrous drug delivery systems have emerged as promising alternative solid-dosage forms due to their advantages of high porosity, high surface to volume ratio, and high drug-loading efficacy. Herein, a number of nanofibrous mats composed of different types of Eudragit® polymers in various concentrations and combinations loaded with furosemide were designed, successfully electrospun, and characterized using SEM, FTIR, DSC, and TGA analyses. The nanofibrous nonwovens were formulated in nanofiber tablets and the release profile of furosemide from them was evaluated at pH 1.2 and 6.8 and compared to that of physical mixture matrix tablets of analogous composition as well as to that of a commercial formulation. It was found that the release of furosemide was compatible with the gastroretentive and slower intestinal release requirements with a well-defined absorption window, while some nanofiber formulations could act as furosemide carriers in emergency situations where a relatively fast onset of its action is required, as in the case of critically ill post-traumatic patients.

Highlights

Furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid, Figure 1), belonging to the chemical class of aminobenzenesulfonamides, is a chloride channel blocker, ordinarily used as a high-ceiling or loop diuretic [1,2,3]
In the framework of this study, furosemide was successfully incorporated through electrospinning into micro/nano non-woven fibers composed of various types of Eudragit®
The chemical integrity of furosemide after the electrospinning process under the applied conditions was verified by 1H NMR and UV/VIS spectroscopic analyses of the recovered compound following the extraction of the prepared fiber mats

Summary

Introduction

Furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid, Figure 1), belonging to the chemical class of aminobenzenesulfonamides, is a chloride channel blocker, ordinarily used as a high-ceiling or loop diuretic [1,2,3]. Being a potent loop diuretic, it is used in the treatment of edema related with congestive heart failure, hepatic cirrhosis, and renal disease including nephrotic syndrome as well as to manage hypertension [4]. 22 ooff 1133 well as to manage hypertension [4]. Its exact mechanism of action is not fully understood [1,4]; hhoowweevveerr,,iitthhaassbbeeeennssuuggggeesstteeddttoo iinnhhiibbiitt tthhee wwaatteerr rreeaabbssoorrppttiioonn iinn tthhee neepphhrroonn bbeeccaauussee iitt bblloocckkss the sodium–potassium–chloride co-transporter in the thick ascending limb, which is responsible for tthhee rreeaabbssoorrppttiioonn.

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