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

Susana Santos Braga,Filipe A Almeida Paz,Firas El-Saleh,Karyna Lysenko

doi:10.3390/molecules26030519

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.

Highlights

IntroductionEfavirenz (EFV) is a potent antiretroviral of widespread use as first-line therapy for patients with HIV infection
Inclusion stoichiometry in solution was first assessed as a means to understand the preferences of this host–guest system
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

Summary

Introduction

Efavirenz (EFV) is a potent antiretroviral of widespread use as first-line therapy for patients with HIV infection. Administered in the form of a tablet and requiring only one dose per day [1], efavirenz is a practical therapeutic option. It is classified by the Biopharmaceutical Classification System (BCS) as a class II drug, that is, it is poorly water soluble and highly permeable [2].

Methods

Results

Conclusion