Experimental and Computational Comparative Study of the Supercritical Fluid Technology (SFT) and Kneading Method in Preparing β-Cyclodextrin Complexes with Two Essential Oils (Linalool and Carvacrol).

Supercritical fluid technology (SFT) offers many advantages as a potential complexation method compared to the conventional kneading technique. Its applicability to processess in which solvents are not required is a significant benefit. The main aim of this study was to evaluate, experimentally and computationally, the applicability of SFT in the preparation of β-cyclodextrin complexes with two selected essential oils, namely, carvacrol and linalool. Preparation of the complexes was performed using kneading and SFT method. Several methods were used in the solid-state characterization. These include thermal analysis, powder X-ray diffraction, Fourier transform infrared spectroscopy, and solid-state nuclear magnetic resonance. Besides, molecular dynamics simulations of all studied systems were conducted in order to have a deeper and a detailed insight, at the atomic level, of the nature of the two used techniques. Despite all the advantages of SFT, better results of guest molecule entrapment inside β-cyclodextrin were obtained with the kneading method. The percentages of oil content for linalool samples were 70 ± 14 and 84 ± 9% for SFT and kneading method, respectively, while the drug content values for carvacrol samples were 67 ± 15 and 81 ± 13% for SFT and kneading method, respectively. Interestingly, simulation results were in perfect agreement with the experimental ones and, moreover, they provided a plausible explanation for the obtained results. In conclusion, our results showed that the SFT was unsuccessful in enhancing the stability of the studied complexes contrary to that of the conventational kneading method, and in both cases, molecular dynamics simulations correctly predicted the expected outcomes.