Supercritical solvent impregnation of sodium valproate nanoparticles on polymers: Characterization and optimization of the operational parameters

Abstract

To improve the bioavailability and reduce the therapeutic dose and side effects of Sodium valproate (S-VPA), nanoparticles of this drug were loaded on the polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) polymers via the supercritical solvent impregnation (SSI) process. This process was carried out at different pressures (150–250 bar), temperatures (308–328 K), and impregnation times (60–180 min). The Box–Behnken design (BBD) method was applied to study the effect of operational parameters on the S-VPA/PVP and S-VPA/HPMC loadings and optimize the condition. Maximum loadings on both PVP (1.56%) and HPMC (1.5%) were achieved at 250 bar, 318 K, and 180 min. Moreover, the impregnated samples (S-VPA/PVP and S-VPA/HPMC) were investigated by the FTIR, DSC, SEM, DLS, and XRD analysis. The S-VPA nanoparticles with the mean particle size of 27 nm and 128 nm were uniformly impregnated on the PVP and HPMC polymers, respectively. The results confirmed the lower crystallinity of the impregnated S-VPA nanoparticles, leading to their higher solubility and bioavailability. Finally, Enhanced S-VPA solubility was approved by comparing the dissolution rate of the original and the impregnated S-VPA samples in the optimum conditions.