Quality by design-guided development of silica-enabled lipid hybrid nanoparticles for enhanced olaparib dissolution

Olaparib (OLA), a poorly water-soluble anticancer drug (0.0601 mg/mL) with limited oral bioavailability (>50%), belongs to Biopharmaceutics Classification System (BCS) class IV and requires advanced formulation strategies to improve its biopharmaceutical performance. This study developed and optimised OLA-loaded silica-enabled lipid hybrid nanoparticles (SLHNs) using a quality by design (QbD) approach. The lipid hybrid nanosystem was prepared by the melt emulsification method and converted into free-flowing SLHN powder by impregnation onto mesoporous silica carrier Parteck^® SLC. Screening studies, supported by molecular docking and solubility assessment, selected Capmul^® MCM, Cremophor^® RH40, and Transcutol^® HP as the oil, surfactant, and co-surfactant, respectively. Pseudo-ternary phase diagram analysis showed a broad nanoemulsion region at a Smix ratio of 3:1. Plackett-Burman screening identified oil concentration, Smix concentration, and stirring time as critical factors influencing globule size (41.67 ± 0.73 to 154 ± 2.35 nm), polydispersity index (0.183 ± 0.017 to 0.621 ± 0.018), optical transmittance (91.10 ± 0.889% to 99.83 ± 0.404%), and zeta potential (-17.2 ± 0.34 to -37.7 ± 0.37 mV). The optimised SLHNs showed rapid self-emulsification, nanosized globules, high clarity, and improved dissolution with 30% burst release followed by sustained release up to 2.5 h.