Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility

Abstract

Efavirenz is an antiretroviral drug of widespread use in the management of infections with human immunodeficiency virus type 1 (HIV-1). Efavirenz is also used in paediatrics, but due to its very poor aqueous solubility the liquid formulations available resort to oil-based excipients. In this report we describe the interaction of γ-cyclodextrin with efavirenz in solution and in the solid state. In aqueous solution, the preferential host–guest stoichiometry was determined by the continuous variation method using 1H NMR, which indicated a 3:2 host-to-guest proportion. Following, the solid inclusion compound was prepared at different stoichiometries by co-dissolution and freeze-drying. Solid-state characterisation of the products using FT-IR, 13C{1H} CP-MAS NMR, thermogravimetry, and X-ray powder diffraction has confirmed that the 3:2 stoichiometry is the adequate starting condition to isolate a solid inclusion compound in the pure form. The effect of γ-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.

Characterization of the Inclusion Complexes of Isothiocyanates with γ-Cyclodextrin for Improvement of Antibacterial Activities against Staphylococcus aureus

“…In fact, due to the effect of γ-CD, the phased mass loss of the γ-CD-ITC inclusion complexes showed an evident slope between 132 °C and 300 °C, which delayed their volatilization. A similar study of the inclusion complex of efavirenz with γ-CD was reported by Braga et al [ 36 ]. In addition, both BITC and carvacrol inclusion complexes encapsulated in β-CD have high thermal stabilities [ 34 , 37 ].…”

Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization

“…FT-IR is widely used to analyze the interactions between guest molecules and CD in the solid-state (Braga et al. 2021 ). FT-IR spectra of the raw KME, HP-β-CD, physical mixtures, and KME/HP-β-CD were shown in Figure 4(C) .…”

A Review of Applications of Solid-State Nuclear Magnetic Resonance (ssNMR) for the Analysis of Cyclodextrin-Including Systems

“… 1 H → 13 C CP-MAS NMR spectra of ( a ) Efavirenz (EFV), ( b ) γ-CD, ( c ) (γ-CD) 3 @(EFV) 2 , and ( d ) γ-CD@EFV. Adapted from [ 55 ], licensed under CC BY 4.0. ( e ) Image on the right presents 1 H → 13 C CP NMR pulse sequence.…”