Optimization of Solvent Mixture for Solubilizing Cannabis Extract Using I-Optimal Design

Cannabis extract is a poorly water-soluble but alcohol-soluble substance. The development of a cannabis-based oral spray using a high ethanol concentration could cause oromucosal irritation. Finding a suitable solvent mixture to dissolve cannabis extract is challenging. This work aimed to evaluate the solubilization characteristics of cannabis extract in different solvent mixtures commonly used in oral spray formulations. A 0.1 g sample of cannabis extract, obtained through supercritical carbon dioxide fluid extraction and containing 14.09% cannabidiol and 34.19% ∆9-tetrahydrocannabinol, was dissolved in 1 g of a solvent mixture. The mixture of three solvents (ethanol, propylene glycol, and water) was varied using an I-optimal design. Results showed that the solvent system promoted a clear solution with maximum recovery of cannabidiol and ∆9-tetrahydrocannabinol, composed of 53% ethanol, 35% propylene glycol, and 12% water. This optimized solvent mixture was further verified, and a minor percentage error of less than 10% was achieved, indicating that the software-generated prediction was accurate and reliable. In conclusion, this work clarifies the effect of the solvent mixture on the solubilization characteristics of cannabis extract, which is valuable for the development of a cannabis-based oral spray for the treatment of several ailments.