Rational lipid screening for the development of solid lipid nanoparticles and nanostructured lipid carriers:...

Sertraline hydrochloride, a selective serotonin reuptake inhibitor, suffers from poor aqueous solubility and extensive first-pass metabolism, limiting its oral bioavailability. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) offer a viable strategy to overcome these biopharmaceutical limitations. This study aimed to develop a rational lipid screening approach using Hansen solubility parameters (HSP) combined with experimental validation to identify optimal lipid excipients for sertraline-loaded SLN and NLC formulations. HSP-based theoretical screening was performed for five solid and five liquid lipids, followed by experimental solubility and apparent partition coefficient (P_app) studies. The optimized formulations were prepared via hot homogenization and probe sonication and then characterized for their particle size, PDI, zeta potential, entrapment efficiency (EE%), FTIR, DSC, TEM morphology, in vitro drug release, and three-month storage stability. Precirol^® ATO 5 (Ra = 7.43; solubility 45.6 mg/g) and Capryol^® 90 (Ra = 7.22; solubility 68.9 mg/g) were identified as the most compatible solid and liquid lipids, respectively. The optimized SLN₁ and NLC₃ had particle sizes of 278.42 and 219.74 nm, PDI below 0.26, and zeta potentials of -31.24 and -32.76 mV, respectively. The EE% was 72.45% (SLN₁) and 81.27% (NLC₃). FTIR and DSC confirmed the drug-excipient compatibility and molecular drug dispersion. Drug release followed Korsmeyer-Peppas kinetics, with NLC₃ showing sustained release for up to 48 h. Both formulations were stable under refrigerated conditions. The rational HSP-guided lipid screening strategy successfully facilitated the development of stable, high-performance sertraline HCl-loaded SLN and NLC systems with improved encapsulation and controlled drug release potential.