Formulation and Evaluation of a Furosemide Nanosuspension Using High-Pressure Homogenization for Enhanced Dissolution Rate

Abstract

This study addresses the significant biopharmaceutical challenges of furosemide, a Biopharmaceutics Classification System
(BCS) Class IV drug, by developing a nanosuspension to enhance its dissolution rate. Furosemide nanosuspensions were
produced using high-pressure homogenization (HPH), a robust top-down nanosizing technique, with Poloxamer 407 as
a steric stabilizer. A systematic optimization was conducted using a 3² full factorial design, investigating the effects of
stabilizer concentration (X1: 2%, 3.5%, 5% w/v) and homogenization pressure (X2: 500, 750, 1000 bar) on the formulation’s
critical quality attributes. The optimized formulation (FH5), prepared with 3.5% (w/v) Poloxamer 407 at 750 bar, yielded
nanoparticles with a mean particle size of 347.8±4.6 nm, a narrow size distribution (polydispersity index of 0.149±0.034),
and a zeta potential of −37.8±3.4 mV, indicating good physical stability. This formulation also achieved a high drug content
of 93.0±5.8%. Crucially, in vitro dissolution studies in simulated gastric fluid (pH 1.2) demonstrated a profound enhancement
in dissolution, with 94.58±0.35% of the drug released within 10 minutes, compared to the practical insolubility of the bulk
drug. Drug release kinetics were best described by a Zero-order model, governed by Fickian diffusion. These findings
demonstrate that HPH is a highly effective strategy for producing a stable furosemide nanosuspension, offering significant
potential to improve the oral bioavailability of this therapeutically important compound.