Stability-Indicating RP-HPLC Method Development and Validation for Ibuprofen Across Three Advanced Drug Delivery Systems: Liposomes, PLGA Nanoparticles and a Transdermal Patch

Advanced drug delivery systems (ADDS) — liposomes, polymeric nanoparticles and transdermal patches — markedly improve the pharmacokinetic and targeting profile of poorly soluble drugs, yet the absence of validated, stability-indicating analytical methods (SIAMs) for these complex matrices remains a significant barrier to their regulatory approval and routine quality control [1,6,9]. This study developed and validated a reversed-phase high-performance liquid chromatography (RP-HPLC) SIAM for ibuprofen — a Biopharmaceutics Classification System (BCS) Class II model drug — formulated as three distinct ADDS platforms: liposomes prepared by thin-film hydration and membrane extrusion, poly(lactic-co-glycolic acid) (PLGA) nanoparticles prepared by nanoprecipitation, and a matrix-type transdermal patch prepared by solvent casting. All three formulations were physicochemically characterised and subjected to forced degradation under acidic, alkaline, oxidative, photolytic and thermal stress per ICH Q1A(R2)/Q1B guidance. The developed RP-HPLC method resolved ibuprofen from five structurally distinct degradation products and was fully validated per ICH Q2(R2) (linearity r² = 0.99999 over 5–200 μg/mL; accuracy 99.4–100.1%; precision %RSD ≤ 0.78%; LOD 0.24 μg/mL; LOQ 0.71 μg/mL). Six-month long-term and accelerated stability studies demonstrated that all three ADDS retained ≥ 92% assay, with first-order degradation kinetics predicting shelf lives of 27–39 months. Strong inverse correlations (r = −0.92 to −0.96) linked chemical degradation to physical critical-quality-attribute (CQA) drift, together providing an integrated chemo-physical quality-assurance template applicable to ADDS development more broadly.