Preformulation Studies of Furosemide-Loaded Electrospun Nanofibrous Systems for Buccal Administration

Abstract

Abstract:Furosemide loaded electrospun fibers were prepared for buccal administration, with the aim of improving the oral bioavailability of the poorly soluble and permeable crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, poly (vinylpyrrolidone) (PVP) was used. During the experiments, the total polymer concentration was kept constant at 15% (w/w), and only the ratio of the two polymers (HPC-PVP = 5:5, 6:4, 7:3, 8:2, 9:1) was changed. A combination of rheological measurements with scanning electron microscopic morphological images of electrospun samples was applied for the determination of the optimum composition of the gels for fiber formation. The crystalline-amorphous transition of furosemide was tracked by Fourier transform infrared spectroscopy. A correlation was found between the rheological properties of the polymer solutions and their electrospinnability, and the consequent morphology of the resultant samples. With decreasing HPC ratio of the system, a transition from the spray-dried droplets to the randomly oriented fibrous structures was observed. The results enable the determination of the polymer ratio for the formation of applicable quality of electrospun fibers.

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

“…With the appropriate selection of materials (e.g., polymers, solvents, active agent) and electrospinning parameters (e.g., applied voltage, flow rate, tip-to-collector distance), fibers of diverse morphologies such as core-sheath, porous, or hollow structured can be produced [14]. Furthermore, electrospinning is a controlled and reproducible method that has been applied in recent years with increasing frequency for the preparation of controlled-release amorphous solid dispersions and innovative controlled drug delivery systems [15]. Recently, multi-needle or needleless electrospinning techniques have been utilized to increase the range of applications in comparison to conventional electrospinning, while coaxial and tri-axial electrospinning have been used to generate core-shell and multilayer nanofibrous structures with sophisticated structural features [16,17].…”

Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers

“…Two different solutions were made for the electrospinning process. The composition of the first viscous solution was based on the authors' previous study [11]. The stock solution, containing 1 w/w% furosemide, 1.5 w/w% triethanolamine used as a solubilizer, and purified water as a solvent, was used to prepare a homogeneous solution with magnetic stirring in a dark beaker.…”

“…The stock solution also contained 1 w/w% of the drug and purified water was used as a solvent, by adding NaOH solution during magnetic stirring until total dissolution of the furosemide had been reached; the pH value of the resulting solution was 9.8 ± 0.2 in each prepared sample. Based on our previous study [11], the HPC/PVP w/w ratio was determined at 3/2; on the other hand, enhancement of the total polymer concentration was necessary for proper electrospinning. Thus, the total polymer concentration was chosen as 17 w/w% (composition-NaOH).…”

“…Khandavilli et al prepared high-solubility crystalline hydrates of Na and K furosemide salts to improve the poor solubility behavior [3], while other researchers have created several alternative drug carriers, like supramolecular complexes [4,5], hot-melt extrusion products [6], nanocapsules [7], microspheres [8] and halloysites [9] to overcome the unfavorable drug features. Drug-loaded nanofibrous delivery systems could be a promising alternative in case of furosemide, offering unique properties which contribute to the increase of bioavailability with a highly porous structure and a high surface-area-to-volume ratio, and enabling the preservation of the initially crystalline drug in amorphous form in the fibers, either in solid dispersion or in solid solution [10][11][12]. The most frequently used technique is electrospinning to obtain nanofibers; however, many different methods can be used.…”

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery

“…The process of electrospinning allows for the easy incorporation of active ingredients into the system, allowing for increased drug loading within the nanofibers [104]. This process of producing nanofibers also forms a high porous network of fibers [75,105].…”