Novel Strategy for the Systemic Delivery of Furosemide Based on a New Drug Transport Mechanism

Abstract

We reported a novel transport mechanism of curcumin, independent of improved solubility, which involved direct contact of amorphous solid particles with the cell membrane. This mechanism has potential as a novel systemic delivery system of poorly water-soluble drugs. In this study, the transport mechanism of furosemide (FUR), which is transported by the same novel mechanism, was examined. In vitro cell permeation studies under air-interface conditions (AICs) revealed that the permeation from powders sprayed on cell monolayers was significantly higher than that under liquid-covered conditions (LCCs) from their solutions. The permeation from amorphous solid particles was faster than that from crystals. Similar results were derived from in vitro studies using an artificial membrane, with which the permeation of FUR could be examined without water. These findings clearly indicated that the transport mechanism of FUR is the same as that of curcumin. For the application of this new transport mechanism, the in vivo absorption of FUR was examined after pulmonary insufflation, which allows the solid particles to make direct contact with the epithelial cells. Pulmonary absorption of FUR from the amorphous powder was almost complete and was faster than that after intragastric administration of the solution, suggesting that FUR was absorbed from the lung by the same mechanism as the in vitro study. This new transport mechanism, which is independent of water dissolution, could be exploited to develop a novel delivery system for poorly water-soluble drugs, using pulmonary powder inhalation.

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

“…In previous reports, the mechanism that amorphous solid particles directly interact to the surface of membrane, dissolute and permeate the membrane has been proposed. 25,26) Although the membrane used in the reports was not skin, based on the similar mechanism, drug molecules at the SCL state without vehicle would directly contact to the skin surface and dissolute to the skin. Therefore, the reason that the degree of KET permeation improvement of KET-ETH (2 : 1) SCL from KET-ETH (2 : 1) suspension was lower than that of KET SCL from KET suspension may be contact frequency to the skin surface of molecules was proportional to the molar fraction (KET : ETH = 2 : 1) of the binary SCL.…”

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

“…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].…”

“…Furosemide is practically insoluble in water and dilute acids, while its solubility increases at neutral pH because it is a weakly acidic drug with a pKa of 3.9 [1,2,4,5]. Due to its acidic nature, furosemide is mostly absorbed in the stomach (pH = 1.2) and in the upper small intestine (pH = 6.8–7.4) [1,5].…”

“…As an active substance with poor aqueous solubility and poor permeability, furosemide belongs to class IV of the Biopharmaceutics Classification System (BCS) [1,2,7]. During the last few years, researchers have tried to develop sustained release systems of furosemide in order to improve the effectiveness of the drug.…”

A Novel Approach of CFIA Technique for Assaying of Furosemide (Sulfa Drug) as Antibacterial Agent in Pharmaceutical and Biological Samples Using Potassium Ferricyanide as Oxidizing Agent

“…However, the intense and fast dieresis produced by this drug, has extended its application as a powerful acidic diuretic for diverse treatment in human and veterinary medicine. Furosemide is often classified as a loop diuretic due to its predominate action in the nephron [3][4] .Various analytical methods for determining FUR using many techniques have been described in the literature, electrochemical sensing method [5][6][7], HPLC technique [8][9][10], and spectroscopic methods [11][12]. The method used for the analysis of furosemide in the oxidationreduction reaction of the FUR and the reagent and [K3Fe(CN)6] as an oxidizing agent using the flow injection technique to determine the drug in pharmaceutical preparations and biological samples [13][14][15][16][17] The advantages of this method are that it consumes small amounts of the drug and the reagent, has high repeatability with accurate results obtained, is determined in the visible light range, and is a very simple and stable method for drug determination.…”