PRELIMINARY EVALUATION OF DIFFERENT ANTIOXIDANT EXCIPIENTS TO ESTIMATE THE STABILITY OF CANNABIDIOL IN MEDIUM-CHAIN TRIGLYCERIDES

Cannabidiol (CBD) is a highly lipophilic phytocannabinoid widely formulated in oil-based systems. However, its chemical stability remains a major challenge due to its susceptibility to oxidative, photo-, and thermal degradation. This study investigated the effectiveness of different excipients to preserve CBD content in medium-chain triglycerides (MCT; Miglyol®) during thermally accelerated degradation studies. Samples containing 1 mM of CBD in MCT were prepared with (+)-α-Tocopherol 0.15mM, (+)-α-Tocopherol acetate 0.13 mM, butylated hydroxytoluene (BHT) 0.06 mM, or a combination of BHT and (+)-α-Tocopherol acetate. A blend without selected antioxidants was used as a control. Samples were stored under accelerated conditions (70 ± 2 °C, 45% RH) and analyzed at 0, 15, 30, and 60 days. CBD content (%) was quantified using a validated HPLC-UV-DAD method, and solution color was monitored over time. All prototype batches exhibited progressive CBD degradation during the accelerated studies, with the degradation rate being strongly influenced by the type of antioxidants used. After 60 days, the control formulation retained approximately 75% of its initial CBD content. (+)-α-Tocopherol acetate and (+)-α-Tocopherol provided moderate stabilization, preserving approximately 79% and 80% of the initial CBD concentration, respectively. BHT demonstrated the highest individual protective effect, with ca. 86% CBD recovery (***p < 0.001). The combination of BHT and (+)-α-Tocopherol acetate showed a similar protective effect, with 85-87% of CBD remaining after accelerated thermal degradation. Moreover, the oil solution with greater CBD loss exhibited more pronounced color changes, suggesting the formation of degradation products. BHT significantly improved CBD stability in MCT systems under accelerated thermal degradation conditions, either alone or in combination with (+)-α-Tocopherol acetate. These results demonstrate that excipient selection is a critical formulation parameter and support the use of BHT-based antioxidant systems to extend the shelf-life and long-term stability of CBD pharmaceutical products.