Formulation and Evaluation of Furosemide Nanosuspensions by High-Speed Homogenization: An Approach to Enhance Dissolution Rate

Abstract

This research focused on developing and assessing a furosemide nanosuspension to improve its dissolution rate, a key
obstacle to its oral bioavailability, using a high-speed homogenization method. As a Biopharmaceutics Classification System
(BCS) Class IV drug, furosemide’s poor solubility in water and highly inconsistent absorption create major challenges for
reliable therapeutic delivery. We prepared nanosuspensions through high-speed homogenization, a top-down particle
size reduction method, using Poloxamer 407 as a steric stabilizer. To systematically refine the formulation, we applied a 3²
full factorial design, examining how stabilizer concentration (2%, 3.5%, and 5% w/v) and homogenization speed (5,000,
10,000, and 15,000 rpm) affected particle characteristics and drug release. The resulting nanosuspensions underwent
comprehensive characterization, including particle size, polydispersity index (PDI), zeta potential, Scanning Electron
Microscopy (SEM) for surface morphology, and solid-state analysis via Differential Scanning Calorimetry (DSC) and FourierTransform Infrared (FTIR) spectroscopy. The optimized formulation (Fs6), created with 5% w/v Poloxamer 407 at 10,000
rpm, showed a mean particle size of 384 nm, a very low PDI of 0.132, and a zeta potential of -30.7 mV, which suggests good
physical stability. It also contained a high drug content of 95.1%. This formulation achieved a significantly faster dissolution
rate, releasing over 95% of the drug within 10 minutes in simulated gastric fluid (pH 1.2). The release kinetics were best
fitted to the Zero-order model, with Fickian diffusion identified as the underlying release mechanism. Our study confirms
that high-speed homogenization is a viable and scalable technique for creating stable furosemide nanosuspensions. The
remarkable improvement in dissolution points to a promising path for boosting the oral bioavailability of furosemide and
other difficult BCS Class IV drugs.