Matrix-dependent degradation kinetics and impurity fingerprinting of cannabidiol (CBD) in polymeric and lipid preservation systems

Cannabidiol (CBD), a non-psychoactive terpenophenolic compound derived from Cannabis sativa , exhibits broad-spectrum pharmacological activities but is highly susceptible to oxidative, photolytic, and thermal degradation, making it challenging to preserve and use in therapeutics. Therefore, this study compares the preservation efficiency of a powder-based hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion-complex system for cannabinoid stability and solubility and medium-chain triglyceride (MCT) oil, a common lipid-based carrier in commercial formulations. Formulation characterizations, including CBD content (HPLC), color change, solvent residues, moisture, particle size, and zeta potential, were measured. DPPH experiments revealed that the HP-β-CD complex exhibited higher antioxidant activity (89.2%, EC₅₀ = 45.3 µg/mL) than the MCT oil system (83.6%, EC₅₀ = 58.7 µg/mL), with ascorbic acid serving as the control (EC₅₀ = 12.4 µg/mL). Additionally, photostability testing (8000 lux) demonstrated superior CBD retention in the HP-β-CD complex (>90%) compared with MCT oil (∼20%), indicating substantial light-induced degradation in the oil system. HP-β-CD complex retained 92–93% CBD (k = 0.0084 week⁻¹; t₁/₂ = 82.5 weeks) versus 88% in MCT oil. At 40 °C, HP-β-CD complex preserved 86–87% CBD. GC-FID/GC-MS showed that HP-β-CD powder preserved CBD with only trace degradation (<0.1–1.0%). In contrast, MCT oil produced higher cannabinoid by-products (0.1–6.21%), and greater antioxidant degradation (2.5–8.6% vs 0.5–2.1%). The results suggested that CBD degradation follows matrix-dependent kinetics, with cyclodextrin encapsulation significantly reducing the apparent degradation rate constants relative to oil-based solubilization under identical stress conditions.