ABSTRACT

Hydrochlorothiazide, a poorly soluble and also a poorly permeable drug of BCS class IV, was formulated into solid lipid nanoparticles (SLNs) using the microemulsion method. Precirol® ATO 5, Tween® 80 and Kolliphor® P 188 were employed as lipid, surfactant and co-surfactant, respectively. Optimization using 23 factorial design explored lipid concentration (A), surfactant concentration (B) and stirring time (C) as independent variables, and particle size (Y1), % entrapment efficiency (Y2), and drug release (Y3) as responses. FTIR and DSC demonstrated drug-excipient compatibility. The optimized SLNs showed a 12-fold water solubility increase, 94.75±0.0026 % drug content, 91.23±0.29 % entrapment efficiency, 35.06±0.0019 % drug loading and sustained zero order drug release. A permeation study revealed enhanced flux (166.14±0.013µg cm-2h) and permeability coefficient (83.07±0.031 cm h-1) compared to the pure drug. SEM showed uniform, smooth particles, while XRD confirmed the SLN’s amorphous nature. These results show the potential of SLNs to significantly enhance the hydrochlorothiazide’s solubility and permeability.