QbD-Assisted Development and Optimization of a Finerenone Nanosuspension for Enhanced Solubility

Abstract

Purpose

Finerenone (FN), a selective non-steroidal mineralocorticoid receptor antagonist used for the management of kidney disease, shows poor aqueous solubility and limited oral bioavailability. The present study aimed to develop and optimize a FN-nanosuspension using Quality by Design (QbD) approach to increase its solubility.

Methods

FN-nanosuspension was prepared using an antisolvent precipitation method followed by high-speed homogenization and lyophilisation. The QbD design was applied by describing the Quality Target Product Profile (QTPP), categorizing Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs), and executing a risk assessment. JMP Pro 8 software was used to apply fractional factorial design for the screening of the variables and to identify the significant factors, followed by Box–Behnken Design (BBD) optimization. The prepared formulations were evaluated for particle size, PDI, zeta potential, saturation solubility, and drug content. The optimized formulation was characterized for solid-state properties (DSC, XRD, FTIR), morphology (SEM), residual solvent (GC), in vitro drug release, ex vivo intestinal permeability, and stability.

Results

The optimized FN-nanosuspension displayed a mean particle size of 276.6 ± 4.98 nm, acceptable zeta potential, with narrow PDI (<0.3), indicating good physical stability. Saturation solubility was considerably improved compared to the pure drug. DSC, XRD, and FTIR studies confirmed the partial amorphization of the drug and no interaction between drug and excipient. The optimized nanosuspension demonstrated fast and enhanced in-vitro drug release (>80% within 30 minutes) following Higuchi kinetics, along with a ~1.8-fold increase in drug diffusion by ex vivo study. Stability studies of the lyophilized formulation over six months showed no significant changes in particle size or aggregation.

Conclusion

The QbD-assisted development of FN-nanosuspension successfully enhanced solubility, dissolution rate, and intestinal permeability while ensuring formulation robustness and stability. The study highlights nanosuspension technology as an effective and scalable strategy to improve the oral performance of poorly soluble drugs such as FN.