## 5 Inclusion Complex Formation
Given that the grinding technique does not rely on various solvents, it is regarded as a clean and environmentally sustainable approach. This method is efficacious due to its rapidity, convenience, and high efficiency in the preparation of inclusion complexes, as well as being essential for compounds possessing low solubility, rendering it a lucrative technological option [25; 35]. Moreover, supercritical anti-solvent precipitation is an innovative methodology that predominantly exploits the supernatant characteristics of supercritical liquids under conditions exceeding threshold temperatures and pressures to synthesize inclusion composites, with CO\({}_{2}\) frequently employed as the supercritical fluid [25; 34; 35]. Initially, CO\({}_{2}\) is introduced into a chamber of high pressure covering the guest element and cyclodext, then whisking at the optimum heat. After that, the resulting supernatant is introduced over an appropriate length of time through a pressure device. The precipitated residue is subsequently deposited at the base of the pressure chamber on a stainless-steel sieve (with approximately 0.1 \(\upmu\)m pore sizes) that permits the CO\({}_{2}\) compound to flow. The procedure concludes with rapid decompression to atmospheric pressure, leading to the gasification of CO\({}_{2}\) and its separation from the resultant complex. This technique is effectively used to integrate a significant amount of guest substances into the CD chambers. The utilization of supercritical fluid technology facilitates meticulous control over temperature, pressure, and solute concentration, thereby enhancing the formation of high-quality cyclodextrin complexes [34; 35]. The stability and structure of inclusion complexes have been investigated in a number of earlier investigations using methods like phase X-ray crystallography, NMR spectroscopy, and solubility analysis [11]. A recent conclusion by [PERSON] et al. (2024) revealed that mass spectrometry, NMR spectroscopy, and molecular modelling are the most important tools in analysing the structure and stoichiometry of complexes with inclusion [36], in addition to clarifying the inclusion mechanism [37]. The above techniques offer valuable information about the arrangement of the guest elements inside the cyclodextrin chamber, the potency of the formed complex, and the linked thermodynamic processes. It is plausible that integrating NMR techniques into cyclodextrin research proves highly beneficial for ascertaining bonding strength, the arrangement of guest substances relative to the host, and any structural modifications that occur during the complexity process. These investigations provide a comprehensive overview of how NMR methodologies, such as two-dimensional NMR correlation procedures and cross-polarization magic angle spinning (CP/MAS), can be utilized to obtain more understanding of the cyclodextrin systematic structural features [11; 12; 37]. Moreover, isothermal titration calorimetry (ITC) offers a fresh viewpoint for comprehending how drugs interlink with cyclodext (CDs). This technique can be utilized concurrently to ascertain the stoichiometry of inclusion complexity and to measure thermodynamic parameters, including the complex stability constant (K), as well as the derived average reaction standard of enthalpy (\(\Delta\)rH\({}^{\circ}\)), Gibbs energy (\(\Delta\)rG\({}^{\circ}\)), and entropy (\(\Delta\)rS\({}^{\circ}\)) [36; 38].