Influence of Surfactants on the Stability of Cannabidiol, Formulated as a Water-Soluble Product, in Simulated Gastric Fluid

Abstract

This study explored the degradation of water-soluble cannabidiol (CBD) products in surfactant-containing gastric fluid. It was hypothesized that various surfactants would catalyze CBD degradation, and their chemical properties were investigated in detail. CBD products (CBD oil and two water-soluble CBD products) were dissolved in water containing nine surfactants: C₈H₁₇SO₄Na, C₁₀H₂₁SO₄Na, C₁₂H₂₅SO₄Na (sodium dodecyl sulfate; SDS), C₁₄H₂₉SO₄Na, C₁₆H₃₃SO₄Na, C₁₂H₂₅SO₃Na, C₁₂H₂₅HPO₄Na, polysorbate 80, and benzethonium chloride. Simulated gastric fluid (SGF) was added to each sample, and reactions were performed at 37°C for 15–120 min. Concentrations of CBD and reaction products were analyzed using HPLC coupled with a photodiode array detector. The chromatographic analysis confirmed CBD degradation in the presence of surfactant catalysts such as C₁₄H₂₉SO₄Na, SDS, C₁₂H₂₅SO₃Na, C₁₆H₃₃SO₄Na, and C₁₂H₂₅HPO₄Na (listed in the ascending order of conversion rates). Conversely, no CBD degradation occurred in certain reaction mixtures in SGF. Specifically, other cannabinoids were not detected in samples containing CBD oil with SDS or water-soluble CBD products with C₈H₁₇SO₄Na and C₁₀H₂₁SO₄Na surfactants. Similarly, no conversion was observed with cationic/nonionic surfactants or without surfactants. This study first demonstrated the degradation of CBD in gastric fluid containing surfactants other than SDS. This conversion occurs only when CBD is formulated in water-soluble products. The anionic surfactants soluble in SGF were the most effective surfactant catalysts. While future in vivo studies are necessary, these findings suggest that co-administration of CBD products with anionic surfactants disturbs the dose adjustment of CBD that exhibits high inter-/intra-individual variability and produces other cannabinoids.