Formulation and Evaluation of Proliposomal Drug Delivery System of Furosemide for Enhanced Oral Bioavailability

AbstractThe present study aimed to formulate and evaluate furosemide-loaded proliposomes as a lipidbased drug delivery system to enhance the potential of nanosized vesicular carriers for poorlywater-soluble drugs. Furosemide is a potent loop diuretic characterized by poor aqueoussolubility, which may limit its dissolution and bioavailability. Preformulation studies confirmedthe physical characteristics and poor aqueous solubility of furosemide, with better solubilityobserved in organic solvents, particularly the chloroform system. UV-visible spectrophotometricanalysis established a maximum absorption wavelength (λmax) of 274 nm in phosphate bufferpH 7.4. The calibration curve showed excellent linearity over the concentration range of 5–40µg/mL, with a regression equation of y = 0.0204x + 0.0254 and an R² value of 0.9918. Nineproliposomal formulations (F1–F9) were prepared using furosemide (50 mg), soybean lecithin(100–200 mg), cholesterol (10–30 mg), and D-mannitol as the carrier. Variation in lipidcomposition influenced drug loading, entrapment efficiency, and in vitro drug-releasecharacteristics. Scanning electron microscopy revealed predominantly rounded to nearlyspherical vesicles with defined boundaries, although minor aggregation and surface roughnesswere observed. The optimized formulation exhibited a narrow, predominantly unimodalnanosized particle distribution, with the major population ranging from approximately 90–100nm. Zeta-potential analysis showed a negative surface charge of approximately -22 mV,indicating sufficient electrostatic repulsion that may contribute to improved vesicular dispersionand stability. Overall, the findings demonstrate that furosemide-loaded proliposomes cansuccessfully generate nanosized vesicular systems and represent a promising lipid-basedapproach for improving the delivery characteristics of furosemide.