Strategies to Enhance the Solubility and Oral Bioavailability of Furosemid: A Review

Furosemide is a loop diuretic widely prescribed for the management of edema and hypertension; however, its oral efficacy is limited by poor solubility and low permeability. According to the Biopharmaceutics Classification System, furosemide belongs to class IV, necessitating optimization at the preformulation stage to enhance its biopharmaceutical performance. This review aims to analyze various preformulation strategies that have been demonstrated to improve the solubility and oral bioavailability of furosemide through an extensive literature review of scientific publications from the past decade. The investigated approaches include particle size reduction, co-amorphous systems, micronization, solid dispersion, solvent evaporation, cyclodextrin complexation, pH adjustment, self-nanoemulsifying drug delivery systems, nanostructured lipid carriers, solid–liquid nanoparticles, nanosuspensions, and controlled precipitation methods. The review indicates that these strategies markedly enhance the dissolution rate and physical stability of furosemide through several mechanisms, such as increased surface area, amorphous phase formation, inclusion complexation, and maintenance of supersaturated states. Among the reviewed strategies, lipid-based and nanoscale delivery systems generally demonstrated greater improvements in oral bioavailability than conventional approaches, although direct comparisons should be interpreted with caution because of differences in study design, experimental conditions, and pharmacokinetic endpoints. Overall, physicochemical modification and nanotechnology-based preformulation strategies offer promising potential to overcome the solubility limitations of furosemide, thereby improving oral therapeutic efficacy and reducing interindividual pharmacokinetic variability.