Cyclodextrin-efavirenz complexes investigated by solid state and dissolution studies

Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, is a first-line treatment for adult and pediatric human immunodeficiency virus type 1 infection (HIV-1) both in adults and in children. EFV belongs to class II of Biopharmaceutical Classification System (BCS); that is, it is poorly water-soluble and highly permeable. Approaches to improve efavirenz dissolution include manipulation of polymorphs, the use of superdisintegrants, solid dispersions, nano-sized polymeric micelles and complexation with two derivatives of β-cyclodextrin: RAMEB and HPβCD. Inclusion into cyclodextrins, besides increasing solubility, brings aditional advantages such as taste masking and protection against hydrolytical instability. These will be helpful in creating aqueous pediatric formulations, which are currently unavailable. In the present work, the interaction of efavirenz with beta- and gamma-cyclodextrins is investigated, revealing that only gamma-cyclodextrin has the adequate size to acommodate the bulky molecules of efavirenz. A complete solid-state characterization of the gamma-cyclodextrin complex with efavirenz is presented, as well as the dissolution profile of the complex.