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

**Susana Santos Braga 1,\* , Firas El-Saleh <sup>2</sup> , Karyna Lysenko 1,3 and Filipe A. Almeida Paz <sup>3</sup>**


**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 <sup>1</sup>H 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, <sup>13</sup>C{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.

**Keywords:** cyclodextrin inclusion; solution-phase; solid state; antiretroviral
