Pilot-Scale Preparation of Broad-Spectrum CBD: Extraction Optimization and Purification using Centrifugal Partition Chromatography.

INTRODUCTION

Cannabinoids, a class of compounds found in L., possess a wide range of pharmacological properties. While Δ-tetrahydrocannabinol (Δ-THC) is strictly regulated owing to its psychoactive effects, cannabidiol (CBD), a nonpsychoactive compound, is permitted in certain countries. This study aimed to optimize the preparation of ethanolic cannabis extracts using response surface methodology (RSM) and develop an effective system for removing Δ-THC through centrifugal partition chromatography (CPC) to produce broad-spectrum CBD (hemp extract containing CBD and other compounds with minimal or no Δ-THC).

METHODS

Three variables and six responses were assessed to optimize extraction conditions. Predictions were made using Design-Expert software, and the experimental conditions were identified using the Box-Behnken design (BBD). The extracts were analyzed using high-performance liquid chromatography and a chromameter. Optimal conditions were used for pilot-scale extraction, and the CPC process was optimized by determining the partition coefficient of the target cannabinoids in various solvent systems and maximum sample load.

RESULTS

The optimal extraction conditions were -31°C for 33 min and a sample-to-solvent ratio of 1:8% w/v, with a desirability value of 0.576. Temperature was the most influential factor. Although the total yield decreased, this condition provided the highest concentration of light-colored cannabinoids and was successfully scaled up for the three other cannabis samples. The optimal CPC solvent system, consisting of hexane/0.1% FA in ACN/20 mm ammonium formate at a ratio of 10/6.5/3.5 v/v/v, demonstrated a yield recovery of 89.3 ± 0.21% w/w with a maximum load of 5 g of sample per run. The resulting broad-spectrum CBD extract had a high CBD content (73.3 ± 0.37% w/w) and minimal Δ-THC content (0.2 ± 0.00% w/w).

CONCLUSION

BBD-RSM optimization of ethanolic cannabis extraction provided the highest cannabinoid concentration with a short extraction time and desirable appearance. The CPC process successfully separated Δ-THC, yielding a high-purity broad-spectrum CBD extract.