Amorphous Solid Dispersion/Salt of Efavirenz: Investigating the Role of Molecular Interactions on Recrystallization and In-vitro Dissolution Performance

Abstract

Efavirenz (EFZ), a BCS (Biopharmaceutical classification system) class-II/IV drug, suffers from low oral bioavailability (40–50%) and significant inter/intra-individual variability due to its low solubility and poor dissolution properties. The present investigation aimed to prepare a stable amorphous system of EFZ to improve its dissolution using the slurry method with various polymers and examine the nature of the interaction between them and its impact on the stability (recrystallization) of the formed systems and their in-vitro dissolution performance. Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies proved the formation of a complete amorphous system of EFZ with Eudragit® E100, HPMC E5, and HPMCAS-LF up to 50% drug loading. During 90 days accelerated stability studies, amorphous systems prepared using Eudragit® E100 remained stable at 50% drug loading however those prepared with HPMC E5, and HPMCAS-LF only remained stable at 25% drug loading. The ability of Eudragit® E100 based system to stabilize the drug at higher drug loading was attributed to the formation of stronger ionic interaction as revealed by the Fourier-transform infrared spectroscopy (FTIR) study. During in-vitro dissolution study, Eudragit® E100 based amorphous system generated and maintained significantly higher supersaturation compared to those prepared with HPMC E5, and HPMCAS-LF due to the formation of ionic interaction between EFZ and Eudragit® E100 as revealed by solution ¹H NMR study.

Graphical Abstract