Solid lipid nanoparticles as a drug delivery vehicle for hydrochlorothiazide: Comprehensive formulation, characterization, and in vivo study

The main purpose of this research study was to enhance the solubility and permeability of hydrochlorothiazide (HCTZ), a Biopharmaceutical Classification System (BCS) class IV drug, by formulating it as Solid Lipid Nanoparticles (SLNs). A hot homogenization technique was used to develop solid lipid nanoparticles using Gelucire® 50/13 (lipid) and surfactants (Gelucire® 44/14 and Tween 80). The optimized formulation showed a particle size of 247.74 ± 1.46 nm, an entrapment efficiency of 35.34 ± 1.80 %, and a zeta potential of −26.34 ± 0.03 mV. In vitro drug release studies demonstrated enhanced cumulative drug release of optimized HCTZ SLN as compared to the pure drug (103.94 ± 1.65 % versus 53.17 ± 1.95 % at 8 h). Likewise, the ex vivo permeability study using the intestinal membrane showed a 3.6-fold higher permeability as the flux was found to be 13.574 and 3.715 µg.cm - 2 . h -1 , for optimized HCTZ SLN and the pure drug at 24 h, respectively. Furthermore, in vivo studies in rats showed increased cumulative urine output, diuretic index, and greater diuretic activity. The total amount of drug excreted in the rat urine due to the pure drug was 0.361 mg, and the HCTZ SLN was 0.764 mg, respectively. The excretion rate of pure drug and HCTZ SLN was 0.0018 and 0.0051 mg.h -1 , respectively. The elimination rate constant (K e ), half-life (t 1/2 ), and fraction excreted unchanged in urine (F e ) of the pure drug were 0.1089 h −1 , 6.36 h, and 0.42, respectively, while those for HCTZ SLN were 0.0918 h −1 , 7.55 h, and 0.8989, respectively. The findings indicate that SLNs can improve HCTZ’s oral bioavailability and pharmacokinetic profile, offering a promising alternative to conventional formulations. • Solid lipid nanoparticles enhanced the solubility and intestinal permeability of hydrochlorothiazide. • Stearoyl polyoxyl-32 glycerides (Gelucire® 50/13) improved drug incorporation due to their high solubilization capacity. • Entrapment efficiency, particle size, and zeta potential were significantly influenced by surfactant type and concentration. • The formulation strategy presents a promising platform for improving the oral bioavailability of BCS Class IV drugs.