Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability

Abstract

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

Mucoadhesive Polymeric Films to Enhance Barbaloin Penetration Into Buccal Mucosa: a Novel Approach to Chemoprevention

“…As expected, based on our previous experience (49), no glass transition signal (Tg) or component peaks were observed in the DSC thermograms of Eudragit based films. In Fact, the films are constituted by a complex mixture of substances and each one can influence the Tg of the final film.…”

Engineering of Nanofibrous Amorphous and Crystalline Solid Dispersions for Oral Drug Delivery

“…Electrospinning is a rapid solvent evaporation method and is well suited for drugs with thermal instability and can avoid drug re-crystallization or amorphization during processing [24]. Many polymers have been used to prepare SDs such as poly( N -vinvylpyrrolidone) (PVP) [25], polyethylene glycol (PEG) [26], zein [27], hydroxypropyl methylcellulose (HPMC) [28,29], polycaprolactone [30], and polyacrylic acid [31], expanding the potential of processes used to make SDs from the traditional solvent-based methods [32,33], hot melt extrusion (HME) [34,35,36], spray-drying [22,37], to polymer-based nanofabrication methods such as electrospinning [38,39,40] and other centrifugal spinning based methods [12,13,41,42].…”

Development of a Multifunctional Bioerodible Nanocomposite Containing Metronidazole and Curcumin to Apply on L-PRF Clot to Promote Tissue Regeneration in Dentistry

“…In addition, it is crucial to understand the mechanism by which drugs are released, having developed a complex nanocomposite wherein CUR and MTR are incorporated in lipid nanoparticles and in a hydrophilic matrix, respectively. For this purpose, the most common mathematical models used in dissolution analysis were curve fitted to the experimental data, performing the regression analysis [ 62 ]. Mathematical models considered, such as zero- and first-order, Higuchi, Korsmeyer–Peppas, and Peppas–Sahlin, enable the quantitative interpretation of the values obtained from drug release assay [ 63 ].…”