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

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 gamma-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 H-1 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, C-13{H-1} 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 gamma-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.

Automated summary

This study investigated the interaction between gamma-cyclodextrin and efavirenz in both solution and solid state. The 3:2 host-to-guest stoichiometry was found to be the optimal condition for isolating a solid inclusion compound. The effect of gamma-cyclodextrin on the solubility of efavirenz was examined using the isotherm method.