Utilisation of Design of Experiments Approach to Optimise Supercritical Fluid Extraction of Medicinal Cannabis

Carbon dioxide supercritical fluid extraction (CO₂ SFE) is a clean and cost-effective method of extracting cannabinoids from cannabis. Using design of experiment methodologies an optimised protocol for extraction of medicinal cannabis bud material (population of mixed plants, combined THC:CBD approximately 1:1.5) was developed at a scale of one kg per extraction. Key variables investigated were CO₂ flow rate, extraction time and extraction pressure. A total of 15 batches were analysed for process development using a two-level, full factorial design of experiments for three variable factors over eleven batches. The initial eleven batches demonstrated that CO₂ flow rate has the most influence on the overall yield and recovery of the key cannabinoids, particularly CBD. The additional four batches were conducted as replicated runs at high flow rates to determine reproducibility. The highest extraction weight of 71 g (7.1%) was obtained under high flow rate (150 g/min), with long extraction time (600 min) at high pressure (320 bar). This method also gave the best recoveries of THC and CBD. This is the first study to report the repeated extraction of large amounts of cannabis (total 15 kg) to optimise the CO₂ SFE extraction process for a pharmaceutical product.