**4. Conclusions**

The results described in the present report demonstrated that inclusion of efavirenz into γ-CD occurred both in solution and in the solid state, forming a complex with 3:2 stoichiometry, that is, (γ-CD)3·(EFV)2. The bulky nature of efavirenz, with a quasi-planar central bicyclic benzoxazin-2-one ring, and two substituents, a cyclopropylethynyl and a trifluoromethyl, protruding laterally from the main plane of the rings, implies that a host with a large cavity is required for molecular encapsulation. It is noteworthy that, even though we employed γ-CD, a host with a wide cavity diameter, inclusion required 1.5 host units per each molecule of efavirenz—the host-to-guest stoichiometry of 3:2 is quite rare for γ-CD inclusion complexes.

Powder X-ray diffraction further evidenced that the complex belongs to the isostructural series of γ-CD inclusion complexes with tetragonal symmetry in which the molecules of γ-CD are stacked in infinite channels with the guest molecules located inside. This contributed to the symmetrisation of the environment around the carbons of efavirenz, particularly C1, which is part of a carbonyl group, and that was observed as a single resonance in solid-state NMR and as a blueshifted vibrational band in FT-IR. The solubilising effect of γ-CD over the efavirenz guest was evaluated by collection of the solubility isotherm for this host–guest system to reveal a Bs-type diagram [35], that is, the association with γ-CD increases EFV solubility but only to a certain point, which is followed by a plateau. Besides the solubilising action of γ-CD on efavirenz, its ability to mask the bitter taste of this drug is another attractive application for the inclusion complex that warrants demonstration in future studies.

**Author Contributions:** Conceptualisation, S.S.B.; methodology, S.S.B.; data curation, K.L., F.E.-S., S.S.B.; formal analysis, K.L., F.E.-S., S.S.B.; investigation, K.L., F.E.-S., S.S.B.; writing—original draft preparation, S.S.B.; writing—review and editing, K.L., F.E.-S., S.S.B., F.A.A.P.; supervision, S.S.B., F.A.A.P.; funding acquisition, S.S.B., F.E.-S., F.A.A.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** We acknowledge University of Aveiro and FCT/MCTES (Fundação para a Ciência e a Tecnologia, Ministério da Ciência, da Tecnologia e do Ensino Superior) for financial support for the QOPNA research Unit (FCT UID/QUI/00062/2019), LAQV-REQUIMTE (Ref. UIDB/50006/2020) and CICECO—Aveiro Institute of Materials (UIDB/50011/2020 and UIDP/50011/2020), through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through the operational programme COMPETE 2020, POCI and PORL and FCT through PIDDAC).

**Data Availability Statement:** Solid-state characterisation data is available upon request from the NMR and diffraction services of the University of Aveiro.

**Conflicts of Interest:** The authors declare no conflict of interest.
