Nanoparticulate Solid Dispersion Of Mesoridazine: A Strategy For Enhanced Solubility And Tablet-Based Oral Delivery

Abstract

This study developed and characterized mesoridazine nanoparticles using solvent evaporation and dropping methods to overcome its poor aqueous solubility (94.2 ± 3.1 μg/mL), which limits its antipsychotic efficacy. Solid dispersions were prepared with PEG 4000 and Gelucire® 44/14 at 1:1-1:3 (w/w) ratios and systematically evaluated. DSC and XRD analyses confirmed successful amorphization, with crystalline index reduction from 82% to 11% (*p*<0.01). SEM revealed spherical nanoparticles (189.5 ± 12.4 nm, PDI 0.18 ± 0.03) with homogeneous distribution. The optimized formulation (MPS1, 1:1 PEG 4000) demonstrated a 12.1-fold solubility enhancement (1142.4 ± 28.7 μg/mL, *p*<0.001) compared to pure drug. Tablet formulations containing MPS1 exhibited rapid drug release (98.6 ± 1.2% in 30 min) in 0.75% SLS medium, with release kinetics best fitting the Higuchi model (R²=0.9946) and Korsmeyer-Peppas exponent (*n*=0.62) indicating non-Fickian diffusion. Drug content uniformity exceeded 98% across all batches. Accelerated stability studies (40°C/75% RH, 3 months) confirmed formulation robustness, retaining 97.1 ± 0.8% potency with no significant changes in hardness (3.8 ± 0.2 kg/cm²) or friability (0.02%). These results demonstrate that nanoparticulate solid dispersions significantly enhance mesoridazine's biopharmaceutical properties, offering a clinically viable strategy for improved psychiatric therapy through: marked solubility enhancement via nanonization, rapid tablet dissolution meeting USP requirements, and excellent physical and chemical stability. The methodology presents scalable production potential for industrial translation.