Strategic Development of Sertraline Loaded Nanocarrier Systems for Enhanced Solubility

Sertraline hydrochloride, a widely prescribed selective serotonin reuptake inhibitor (SSRI), exhibits poor aqueous solubility and pH-dependent precipitation, leading to dissolution-limited absorption and variable oral bioavailability. Although several formulation approaches have been explored, comparative evaluation of advanced lipid-based nanocarriers for sertraline hydrochloride remains limited. The present study focuses on the strategic development of solid lipid nanoparticles (SLNs) and lipid–polymer hybrid nanoparticles (LPHNs) to enhance the dissolution behaviour of sertraline hydrochloride. Preliminary investigations, including preformulation studies, analytical method development, and initial formulation trials, confirmed the feasibility of both nanocarrier systems. The formulations will be systematically optimized using a Design of Experiments (DoE) approach and comparatively evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, dissolution behaviour, precipitation inhibition, and physical stability. The study is expected to identify an optimized lipid-based nanocarrier system for sertraline hydrochloride and provide a rational formulation strategy for improving the oral delivery of poorly water-soluble drugs.